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1
Alloway, K. D., M. J. Johnson, and M. B. Wallace. "Thalamocortical interactions in the somatosensory system: interpretations of latency and cross-correlation analyses." Journal of Neurophysiology 70, no. 3 (September 1, 1993): 892–908. http://dx.doi.org/10.1152/jn.1993.70.3.892.
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1. Isolated extracellular neuronal responses to cutaneous stimulation were simultaneously recorded from corresponding peripheral representations in the ventrobasal nucleus and primary somatosensory cortex of intact, halothane-anesthetized rats. Thalamic and cortical neurons representing hairy skin on the forelimb were activated by hair movements produced by a series of 50 or 100 discrete air jets. A corresponding set of neurons representing the glabrous pads of the hind paw were activated by a similar number of punctate mechanical displacements. 2. Cortical electrode penetrations were histologically reconstructed, and 118 neurons in the glabrous skin representation exhibited cutaneous responses that were categorized into supragranular, granular, or infragranular groups according to their laminar position. Minimum latencies of cortical neurons responding to glabrous skin displacement were analyzed, and significant differences were found in the distribution of minimum latencies for the different cortical layers. Mean values for minimum latencies in the infragranular and granular layers were 15.8 and 16.3 ms, respectively, whereas supragranular neurons were characterized by minimum latencies having a mean of 20 ms. The differences between these groups suggests that stimulus-induced afferent activity reaches infragranular and granular layers before contacting supragranular neurons. Average latencies were also calculated on responses occurring during the 1st 20 trials, but the cortical distributions of these values overlapped considerably, and differences between the laminar groups were not statistically significant. 3. In several recording sites, two cortical neurons were recorded simultaneously, and the response latencies of these matched pairs were often substantially different despite the similarity in laminar position. This result indicates that laminar location is not the only determinant of response latency and that serially organized circuits are distributed within, as well as between, cortical layers. 4. From a sample of 302 neurons exhibiting cutaneous responses within histologically identified regions of thalamus or cortex, a set of 143 pairs of neurons recorded simultaneously from both regions was available for cross-correlation analysis. Significant thalamocortical interactions were found in 38 neurons pairs. Analysis of these significant interactions revealed that thalamocortical connection strength, as measured by neuronal efficacy, was two to four times larger for neuron pairs having the cortical cell in granular layer IV than for neuron pairs having an extragranular layer cortical neuron. There was no difference in thalamocortical connection strength between neuron pairs containing supra- or infragranular cortical neurons. 5. Summed peristimulus time histograms revealed stimulus-locked inhibition of spontaneous activity in 4% (8/195) or cortical and 18% (20/107) of thalamic neurons.(ABSTRACT TRUNCATED AT 400 WORDS)
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Sajjad, Hassan, Nadir Durrani, and Fahim Dalvi. "Neuron-level Interpretation of Deep NLP Models: A Survey." Transactions of the Association for Computational Linguistics 10 (2022): 1285–303. http://dx.doi.org/10.1162/tacl_a_00519.
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Abstract The proliferation of Deep Neural Networks in various domains has seen an increased need for interpretability of these models. Preliminary work done along this line, and papers that surveyed such, are focused on high-level representation analysis. However, a recent branch of work has concentrated on interpretability at a more granular level of analyzing neurons within these models. In this paper, we survey the work done on neuron analysis including: i) methods to discover and understand neurons in a network; ii) evaluation methods; iii) major findings including cross architectural comparisons that neuron analysis has unraveled; iv) applications of neuron probing such as: controlling the model, domain adaptation, and so forth; and v) a discussion on open issues and future research directions.
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Collins, Christine E., Emily C. Turner, Eva Kille Sawyer, Jamie L. Reed, Nicole A. Young, David K. Flaherty, and Jon H. Kaas. "Cortical cell and neuron density estimates in one chimpanzee hemisphere." Proceedings of the National Academy of Sciences 113, no. 3 (January 4, 2016): 740–45. http://dx.doi.org/10.1073/pnas.1524208113.
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The density of cells and neurons in the neocortex of many mammals varies across cortical areas and regions. This variability is, perhaps, most pronounced in primates. Nonuniformity in the composition of cortex suggests regions of the cortex have different specializations. Specifically, regions with densely packed neurons contain smaller neurons that are activated by relatively few inputs, thereby preserving information, whereas regions that are less densely packed have larger neurons that have more integrative functions. Here we present the numbers of cells and neurons for 742 discrete locations across the neocortex in a chimpanzee. Using isotropic fractionation and flow fractionation methods for cell and neuron counts, we estimate that neocortex of one hemisphere contains 9.5 billion cells and 3.7 billion neurons. Primary visual cortex occupies 35 cm2 of surface, 10% of the total, and contains 737 million densely packed neurons, 20% of the total neurons contained within the hemisphere. Other areas of high neuron packing include secondary visual areas, somatosensory cortex, and prefrontal granular cortex. Areas of low levels of neuron packing density include motor and premotor cortex. These values reflect those obtained from more limited samples of cortex in humans and other primates.
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Medini, Chaitanya, Bipin Nair, Egidio D'Angelo, Giovanni Naldi, and Shyam Diwakar. "Modeling Spike-Train Processing in the Cerebellum Granular Layer and Changes in Plasticity Reveal Single Neuron Effects in Neural Ensembles." Computational Intelligence and Neuroscience 2012 (2012): 1–17. http://dx.doi.org/10.1155/2012/359529.
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The cerebellum input stage has been known to perform combinatorial operations on input signals. In this paper, two types of mathematical models were used to reproduce the role of feed-forward inhibition and computation in the granular layer microcircuitry to investigate spike train processing. A simple spiking model and a biophysically-detailed model of the network were used to study signal recoding in the granular layer and to test observations like center-surround organization and time-window hypothesis in addition to effects of induced plasticity. Simulations suggest that simple neuron models may be used to abstract timing phenomenon in large networks, however detailed models were needed to reconstruct population coding via evoked local field potentials (LFP) and for simulating changes in synaptic plasticity. Our results also indicated that spatio-temporal code of the granular network is mainly controlled by the feed-forward inhibition from the Golgi cell synapses. Spike amplitude and total number of spikes were modulated by LTP and LTD. Reconstructing granular layer evoked-LFP suggests that granular layer propagates the nonlinearities of individual neurons. Simulations indicate that granular layer network operates a robust population code for a wide range of intervals, controlled by the Golgi cell inhibition and is regulated by the post-synaptic excitability.
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Zhang, Mengliang, and Kevin D. Alloway. "Stimulus-Induced Intercolumnar Synchronization of Neuronal Activity in Rat Barrel Cortex: A Laminar Analysis." Journal of Neurophysiology 92, no. 3 (September 2004): 1464–78. http://dx.doi.org/10.1152/jn.01272.2003.
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We used cross-correlation analysis to characterize the coordination of stimulus-induced neuronal activity in the primary somatosensory barrel cortex of isoflurane-anesthetized rats. On each trial, multiple whiskers were simultaneously deflected at frequencies that corresponded to 2, 5, 8, or 11 Hz. Among 476 neuron pairs that we examined, 342 (71.8%) displayed significant peaks of synchronized activity that exceeded the 99.9% confidence limits. The incidence and strength of these functional associations varied across different cortical layers. Only 52.9% of neuron pairs in layer IV displayed synchronized responses, whereas 84.1% of the infragranular neuron pairs were synchronized during whisker stimulation. Neuronal synchronization was strongest in the infragranular layers, weakest in layer IV, and varied according to the columnar configuration of the neuron pairs. Thus correlation coefficients were largest for neuron pairs in the same whisker barrel row but were smallest for neurons in different rows and arcs. Spontaneous activity in the infragranular layers was also synchronized to a greater degree than in the other layers. Although infragranular neuron pairs displayed similar amounts of synchronization in response to each stimulus frequency, granular and supragranular neurons were synchronized mainly during stimulation at 2 or 5 Hz. These results are consistent with previous studies indicating that infragranular neurons have intrinsic properties that facilitate synchronized activity, and they suggest that neuronal synchronization plays an important role in transmitting sensory information to other cortical or subcortical brain regions.
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Conrad, Rachel, and Mia C. N. Perez. "Congenital Granular Cell Epulis." Archives of Pathology & Laboratory Medicine 138, no. 1 (January 1, 2014): 128–31. http://dx.doi.org/10.5858/arpa.2012-0306-rs.
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Congenital granular cell epulis is a rarely reported lesion of unknown histogenesis with a strong predilection for the maxillary alveolar ridge of newborn girls. Microscopically, it demonstrates nests of polygonal cells with granular cytoplasm, a prominent capillary network, and attenuated overlying squamous epithelium. The lesion lacks immunoreactivity for S-100, laminin, chromogranin, and most other markers except neuron-specific enolase and vimentin. Through careful observation of its unique clinical, histopathologic, and immunohistochemical features, this lesion can be distinguished from the more common adult granular cell tumor as well as other differential diagnoses.
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Cavaliere, Antonio, Angelo Sidoni, Ivana Ferri, and Brunangelo Falini. "Granular Cell Tumor: An Immunohistochemical Study." Tumori Journal 80, no. 3 (June 1994): 224–28. http://dx.doi.org/10.1177/030089169408000312.
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Aims and background Granular cell tumor, usually a benign neoplasm, has been the object of many studies because of its uncertain histogenesis and based on many immunohistochemical and ultrastructural studies it has been suggested that it originates from the Schwann cell. Our recent observation that granular cell tumor is positive with PG-M1, a new anti-macrophage monoclonal antibody, led us to further investigate the immunophenotypic profile of the tumor. Study design We studied 11 granular cell tumors using a panel of 20 antibodies, 13 monoclonal and 7 polyclonal. Results The immunohistochemical study showed in all cases a constant diffuse positivity for S-100 protein, neuron-specific enolase, vimentin, KP1 and PG-M1, as well as occasional and focal positivity for alpha-1-antitrypsin, alpha-1-antichymotrypsin and lysozyme. Conclusions The immunophenotypic profile constantly observed could be the expression, on one hand, of the neuroectodermic nature of the neoplasm, proven by positivity for S-100 protein, neuron specific enolase and vimentin, and on the other could be the expression of the phagocytic activity of the tumor cell, proven by positivity for KP1 and PG-M1 antibodies and also by the presence of numerous phagolysosomes.
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Howarth, Clare, Claire M. Peppiatt-Wildman, and David Attwell. "The Energy Use Associated with Neural Computation in the Cerebellum." Journal of Cerebral Blood Flow & Metabolism 30, no. 2 (November 4, 2009): 403–14. http://dx.doi.org/10.1038/jcbfm.2009.231.
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The brain's energy supply determines its information processing power, and generates functional imaging signals, which are often assumed to reflect principal neuron spiking. Using measured cellular properties, we analysed how energy expenditure relates to neural computation in the cerebellar cortex. Most energy is used on information processing by non-principal neurons: Purkinje cells use only 18% of the signalling energy. Excitatory neurons use 73% and inhibitory neurons 27% of the energy. Despite markedly different computational architectures, the granular and molecular layers consume approximately the same energy. The blood vessel area supplying glucose and O2 is spatially matched to energy consumption. The energy cost of storing motor information in the cerebellum was also estimated.
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Rosso, Renato, Mario Scelsi, and Luciano Carnevali. "Granular Cell Traumatic Neuroma." Archives of Pathology & Laboratory Medicine 124, no. 5 (May 1, 2000): 709–11. http://dx.doi.org/10.5858/2000-124-0709-gctn.
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Abstract Background.—Granular cell changes can be observed in a variety of benign and malignant tumors, and are seen more commonly in granular cell tumors, which in about 5% of cases develop in the breast. Granular cells also have been observed in sites of previous trauma, such as surgery, and are found to be inflammatory reactions of histiocytic origin. Methods and Results.—We investigated, morphologically and immunohistochemically, 2 granular cell lesions occurring in mastectomy scars after surgery for carcinoma. Both lesions were composed of strands and nests of large granular cells, haphazardly set in a background of fibrous tissue, with sparse inflammatory infiltrates. Several tortuous hypertrophic nerve bundles were also embedded in the fibrous tissue. A few of these nerve bundles showed degenerative changes and contained granular cells. Immunohistochemically, granular cells were positive for S100 protein, neuron-specific enolase, vimentin, and CD68 antigen. Conclusions.—We consider these proliferative lesions of peripheral nerves to have the features of both granular cell tumor and traumatic neuroma. These cases indicate that traumatic neuroma can undergo extensive granular cell changes and constitute a previously unrecognized entity, which we provisionally label granular cell traumatic neuroma. Granular cell traumatic neuroma has to be taken into consideration when evaluating lesions occurring at mastectomy scars and should be differentiated from malignant tumors with granular cells, such as apocrine carcinoma and alveolar soft part sarcoma.
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Artuković, Branka, Andrea Gudan Kurilj, Ivana Mihoković Buhin, Lidija Medven Zagradišnik, Ivan-Conrado Šoštarić-Zuckermann, and Marko Hohšteter. "Granular cell tumor in the central nervous system of a ferret (Mustela putorius furo) - a case report." Veterinarski arhiv 92, no. 2 (April 29, 2022): 205–12. http://dx.doi.org/10.24099/vet.arhiv.1705.
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A granular cell tumor (GCT) in the central nervous system (CNS) of a ferret is a rare finding. In this case a cerebral GCT is described in a 5-year-old castrated female ferret. The animal developed lameness in right hind leg which progreseed to total ataxia. The animal died and a necropsy revealed the mass in the medial to caudal part of the left frontal lobe of the brain. Based on histological and imunohistochemical findings, tumor was diagnosed as granular cell tumor. Immunohistochemically, granular cells were diffusely positive for vimentin and neuron-specific enolase (NSE) and weakly focal reactivity for S-100 protein was seen. Neoplastic cells did not express cytokeratins and glial fibrillary acidic protein (GFAP). Although immunohistochemistry was performed, histogenesis of this tumor remains unsolved and controversial.
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Kawaida, Masahiro, Hiroyuki Fukuda, and Naoyuki Kohno. "Granular Cell Tumors Arising Nearly Simultaneously in the Larynx and Subcutaneous Cervical Region." Ear, Nose & Throat Journal 79, no. 3 (March 2000): 162–66. http://dx.doi.org/10.1177/014556130007900309.
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Granular cell tumors are benign, relatively rare lesions that can occur in any organ in the body. Tumors are known to occasionally arise in two or more different organs. We report the case of a 60-year-old woman in whom granular cell tumors arose almost simultaneously in her subcutaneous cervical region and her larynx. The two tumors were surgically resected and examined histopathologically, and they exhibited the same histopathologic features. The tumor of the larynx was resected with the help of a carbon dioxide laser. Immunohistochemical staining revealed that both were positive for S-100 protein and neuron-specific enolase. Cases of the nearly simultaneous appearance of granular cell tumors in the neck and larynx are rather unusual. The results of immunohistochemical staining suggested that this tumor originates in nerve tissue.
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Alp, Murat, and Francis A. Cucinotta. "Biophysics Model of Heavy-Ion Degradation of Neuron Morphology in Mouse Hippocampal Granular Cell Layer Neurons." Radiation Research 189, no. 3 (March 2018): 312–25. http://dx.doi.org/10.1667/rr14923.1.
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Jolly, R. D., A. C. Johnstone, E. J. Norman, J. J. Hopwood, and S. U. Walkley. "Pathology of Mucopolysaccharidosis IIIA in Huntaway Dogs." Veterinary Pathology 44, no. 5 (September 2007): 569–78. http://dx.doi.org/10.1354/vp.44-5-569.
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Dogs with mucopolysaccharidosis (MPS) IIIA were bred within an experimental colony. As part of characterizing them as a model for testing therapeutic strategies for the analogous disease of children, a pathologic study was undertaken. By histology, there were variably stained storage cytosomes within neurons, including many that stained for gangliosides. On ultrastructure examination, these cytosomes contained either moderately dense granular material, tentatively interpreted as precipitated glycosaminoglycan; a variety of multilaminar bodies, interpreted as being associated with secondary accumulation of gangliosides; or a mixture of both types. In the liver, storage vesicles also contained excess glycogen as a secondary storage product. In various tissues, there were large foamy macrophages. In the brain, many of these were in juxtaposition with neurons, and, on ultrastructure examination, they contained storage cytosomes similar to those in neurons. However, the neuron in association with such a macrophage frequently showed little such material.
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Berenguer, J., A. Herrera, L. Vuolo, B. Torroba, F. Llorens, L. Sumoy, and S. Pons. "MicroRNA 22 Regulates Cell Cycle Length in Cerebellar Granular Neuron Precursors." Molecular and Cellular Biology 33, no. 14 (May 13, 2013): 2706–17. http://dx.doi.org/10.1128/mcb.00338-13.
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Wang, J., L. Sun, and Z. Tian. "131. Interferon-gamma, sonic hedgehog signaling and granular neuron precursor proliferation." Brain, Behavior, and Immunity 23 (July 2009): S61. http://dx.doi.org/10.1016/j.bbi.2009.06.136.
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Dimov, D., T. Dikov, L. Dimitrova, C. Filipov, and I. Raychev. "First report of canine mammary gland granular cell tumour: case description and review of the literature." BULGARIAN JOURNAL OF VETERINARY MEDICINE 22, no. 3 (September 2019): 359–67. http://dx.doi.org/10.15547/bjvm.2111.
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The case of a 5-year-old intact female Pitbull Terrier with a granular cell tumour (GCT) of the mammary gland is presented. The dog was admitted for surgical removal of a non-painful lump assumed to be a fibroadenoma. Histological and immunohistochemical findings leading to the diagnosis consisted of polygonal tumour cells with well-defined cell borders and granular cytoplasm, staining positively with neuron-specific enolase (NSE) and protein S100 and negatively for cytokeratin AE1-AE3. Some important points in the diagnostic and therapeutic approach to this uncommon neoplasm are discussed. To our best knowledge this is the first case of such tumour in the mammary gland described in the veterinary literature.
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Li, Chenyang, Tongchuang Lu, Chengfang Pan, and Changlong Hu. "Glucocorticoids Selectively Inhibit Hippocampal CA1 Pyramidal Neurons Activity Through HCN Channels." International Journal of Molecular Sciences 25, no. 22 (November 7, 2024): 11971. http://dx.doi.org/10.3390/ijms252211971.
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Glucocorticoids are known to influence hippocampal function, but their rapid non-genomic effects on specific neurons in the hippocampal trisynaptic circuit remain underexplored. This study investigated the immediate effects of glucocorticoids on CA1 and CA3 pyramidal neurons, and dentate gyrus (DG) granule neurons in rats using the patch-clamp technique. We found that a 5 min extracellular application of corticosterone significantly reduced action potential firing frequency in CA1 pyramidal neurons, while no effects were observed in CA3 or DG neurons. The corticosterone-induced inhibition in CA1 was blocked by the glucocorticoid receptor antagonist CORT125281, but remained unaffected by the mineralocorticoid receptor antagonist spironolactone. Notably, membrane-impermeable bovine serum albumin-conjugated dexamethasone mimicked corticosterone’s effects on CA1 neurons, which exhibited prominent hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents. Pyramidal neurons in CA3 and granular neurons in the DG showed little HCN channel currents. Corticosterone enhanced HCN channel activity in CA1 neurons via glucocorticoid receptors, and the HCN channel inhibitor ZD7288 abolished corticosterone’s suppressive effects on action potentials. These findings suggest that glucocorticoids selectively inhibit CA1 pyramidal neuron activity through HCN channels, providing new insight into the mechanisms of glucocorticoid action in hippocampal circuits.
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Bouchard, P. R., C. H. Fortna, P. H. Rowland, and R. M. Lewis. "An Immunohistochemical Study of Three Equine Pulmonary Granular Cell Tumors." Veterinary Pathology 32, no. 6 (November 1995): 730–34. http://dx.doi.org/10.1177/030098589503200620.
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Granular cell tumor (GCT) is a morphologic designation for tumors of varied histogenesis. Most GCTs in human beings are derived from Schwann cells, and rat meningeal GCTs are believed to originate in the neural crest. Three equine pulmonary GCTs from aged horses were studied immunohistochemically with primary antibodies directed against vimentin, cytokeratins (AE1/AE3), S-100, Leu 7, desmin, and neuron-specific enolase (NSE) using a steptavidin–biotin procedure. All three tumors stained similarly with strong and diffuse staining of neoplastic cells for vimentin and S-100 and negative staining with all other antibodies. On the basis of the immunohistochemical results and the previously described histologic and ultrastructural characteristics, equine pulmonary GCT is designated as neural crest and possibly Schwann cell derived, similar to GCT in rats and human beings.
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Philbert, M. A., C. M. Beiswanger, T. L. Roscoe, D. K. Waters, and H. E. Lowndes. "Enhanced resolution of histochemical distribution of glucose-6-phosphate dehydrogenase activity in rat neural tissue by use of a semipermeable membrane." Journal of Histochemistry & Cytochemistry 39, no. 7 (July 1991): 937–43. http://dx.doi.org/10.1177/39.7.1865111.
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We examined the histochemical distribution of glucose-6-phosphate dehydrogenase (G6PD) activity in neural tissue using different diffusion barriers. Although polyvinyl alcohol and agar overlays permitted regional localization of G6PD, a semipermeable membrane revealed cellular differences in G6PD activity within populations of neurons. Distribution of G6PD activity in selected regions of the nervous system was examined using the membrane technique. White matter usually exhibited strong G6PD activity. The neuronal somata of the dorsal root ganglia (L4-L6) and anterior horns of the spinal lumbar enlargement demonstrated a variation in activity which was independent of somal size. Satellite cells showed intense activity when the membrane technique was used. Hippocampal pyramidal and granular cells of the dentate gyrus exhibited moderate, uniform G6PD activity, but only weak activity was seen in hippocampal and dentate molecular layers. High levels of activity were observed in the vascular endothelial cells of the brain, spinal cord, and choroid plexus, and in the ependymal cells of the spinal central canal and ventricles of the brain. The superior vestibular nucleus appeared to have little G6PD activity in either the neuron cell bodies or the surrounding parenchyma. The use of a semipermeable membrane for localization of G6PD activity in neural tissues permits enhanced resolution of neuron elements and may provide a more accurate assessment of G6PD activity in histological preparations.
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Kreiner, T., W. Sossin, and R. H. Scheller. "Localization of Aplysia neurosecretory peptides to multiple populations of dense core vesicles." Journal of Cell Biology 102, no. 3 (March 1, 1986): 769–82. http://dx.doi.org/10.1083/jcb.102.3.769.
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Many neurons in the mollusc Aplysia are identifiable and provide a useful model system for investigating the cellular mechanisms used by the neuroendocrine system to mediate simple behaviors. In this study we determined the subcellular localization of eight Aplysia neuropeptides using immunogold labeling techniques, and analyzed the size distribution of dense core and granular vesicles in peptidergic neurons. Recent observations demonstrate that many neurons use multiple chemical messengers. Thus, an understanding of the functional significance of cotransmitters requires an analysis of their relative subcellular distributions. The peptides are expressed in a subset of neurons, or the exocrine atrial gland, and are primarily localized to dense core vesicles. Multiple regions of precursors which are cleaved into several components are co-localized. Each neuron has a distinct size distribution of peptide-containing dense core vesicles ranging in size from 65 to 600 nm. The atrial gland contains very large (up to 2 micron) peptide-containing granules. Single neurons have multiple populations of granules whose quantal sizes agree with predictions based on physical constraints. Some cells contain very large peptide-containing granules which are found in the cell soma and not in processes. Thus, the genetic determination of neuronal cell type includes not only transmitter choices but also multiple modes of packaging the intercellular messengers.
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Wang, Rui-Yu, Gregory N. Fuller, Teresa McQueen, Yue-Xi Shi, Richard E. Champlin, and Michael Andreeff. "Distribution and Differentiation of Donor-Derived Bone Marrow Stem Cells in Various Areas of the Human Brain." Blood 106, no. 11 (November 16, 2005): 1685. http://dx.doi.org/10.1182/blood.v106.11.1685.1685.
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Abstract Hematopoietic stem cells (HSCs) resident in the bone marrow or in circulation, have shown the capacity of transdifferentiation into mature neuronal lineages in the brain (Joanna E et al, Stem Cells 2004, 22:487–500 and Cogle et al, The Lancet, 2004, 363:1432–1437). To determine whether this phenomenon occurs at different frequencies in different regions of the brain, immunohistochemical staining with anti-neuron antibody (brown nuclear localization) and anti-CD45 antibody (leukocyte marker, red cytoplasm localization) combined with fluorescence in situ hybridization (FISH) (chromosome X and Y), were performed on autopsy samples from different regions of the brain of two leukemia patients who had undergone sex-mismatched bone marrow transplantation to identify donor-derived neuron and donor leukocytes. The regions of human brain analyzed included midbrain, cerebellum, hippocampus, olfactory bulbs, medulla, pons, and parietal cortex. The distribution of donor-derived leukocytes and donor-derived transdifferentiated neuron in various regions of the bone marrow transplanted recipient’s brain was analyzed in two cases. Approximately 16,500–45,720 cells (average 32,300 cells) on each tissue section were analyzed. For the deep hypercellular granular layer and molecular layer of cerebellum about 343,000 cells were analyzed. An increased percentage of donor leukocytes was found in the hippocampus in both cases (0.8% in case 1 and 1.4% in case 2). In case 1, an increased percentage of donor leukocytes were also found in the pons (0.9%) and olfactory bulbs (1.2%). Transdifferentiation of donor-derived bone marrow stem cells was determined by enumeration of donor-derived mature neuronal cells as percentage in total chromosome XY - positive cells in each region of the brain. The frequency of donor-derived neurons was between 0.6% to 1.7% in cerebellum (0.6% in case 1 and 0.7% in case 2), medulla (1.6% in case 1 and 1.0% in case 2), hippocampus (0.7% in case 1 and 0.6% in case 2), and olfactory bulbs (0.8% in case 1). We did not find donor-derived transdifferentiated neuronal cells in the medulla, pons and parietal cortex in both cases. To determine whether CD34+ cells or mesenchymal stem cells (MSC) have higher potential to differentiation into mature neurons, CD34+ cells and MSC were cultured in transwells with mouse brain extract, respectively. The expression level of neuron specific gene was analyzed after 4 days using western blotting. The levels in CD34+ cells were 1.14-fold higher than in MSC. No neuron specific gene expression was found in CD34+ cells and MSC. These results suggested that 1) the different frequencies of donor leukocytes in regions indicate that the engraftment of circulated donor cells is different in different regions of the brain. 2) Donor-derived mature neurons were found in regions of the midbrain, cerebellum, hippocampus and olfactory bulbs. No donor-derived neurons were found in medulla, pons, and parietal cortex in the two cases analyzed. 3) CD34+ cells have higher potential to differentiation into neurons than MSC.
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Komitova, Mila, Ekaterina Perfilieva, Bengt Mattsson, Peter S. Eriksson, and Barbro B. Johansson. "Effects of Cortical Ischemia and Postischemic Environmental Enrichment on Hippocampal Cell Genesis and Differentiation in the Adult Rat." Journal of Cerebral Blood Flow & Metabolism 22, no. 7 (July 2002): 852–60. http://dx.doi.org/10.1097/00004647-200207000-00010.
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The study aimed to elucidate the effects of cortical ischemia and postischemic environmental enrichment on hippocampal cell genesis. A cortical infarct was induced by a permanent ligation of the middle cerebral artery distal to the striatal branches in 6-month-old spontaneously hypertensive rats. Bromodeoxyuridine (BrdU) was administered as 7 consecutive daily injections starting 24 hours after surgery and animals were housed in standard or enriched environment. Four weeks after completed BrdU administration, BrdU incorporation and its co-localization with the neuronal markers NeuN and calbindin D28k, and the astrocytic marker glial fibrillary acidic protein in the granular cell layer and subgranular zone of the hippocampal dentate gyrus were determined with immunohistochemistry and were quantified stereologically. Compared with sham-operated rats, rats with cortical infarcts had a five-to sixfold ipsilateral increase in BrdU-labeled cells. About 80% of the new cells were neurons. Differential postischemic housing did not influence significantly the total number of surviving BrdU-labeled cells or newborn neurons. However, postischemic environmental enrichment increased the ipsilateral generation of astrocytes normalizing the astrocyte-to-neuron ratio, which was significantly reduced in rats housed in standard environment postischemically.
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Ilic, Ivan, Pavle Randjelovic, Ratko Ilic, Lidija Djordjevic, and Danijela Radojkovic. "Granular-cell tumor: A rare variant of mammary tumor." Vojnosanitetski pregled 65, no. 6 (2008): 488–91. http://dx.doi.org/10.2298/vsp0806488i.
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Background. Granular cell tumor (GCT) is a rare variant of mammary tumor beset with diagnostic dilemmas that may be resolved by using numerous, very complex, enzymohistochemical and immunohistochemical methods. Case reports. We reported three female patients 16, 21 and 65 years old, operated on for mammary tumor at the Surgical Clinic of the School of Medicine in Nis, over the period of thirty years, 1977 to 2007. During this period 14.022 mammary tumors were diagnosed, including these three cases. These tumors had benign characteristics, without associated tumors in other localizations. A typical histological feature of GCT was a granular cytoplasm in large ovoid cells, organized like nests or like a trabecular arrangement. The tumors were analyzed by sets of histochemical, enzymohistochemical, immunohistochemical methods as well as ultrastructural examination. Protein, S-100 neuron-specific enolase and vimentin expressed a diffuse and intensive immunohistochemical activity, while expression of estrogen and progesterone receptors, as well as HER-2 oncoprotein was negative. The ultrastructural analysis confirmed that the tumor cells were enriched by lysosomes and consequential disorganization of cytoplasm. Conclusion. The reported enzymo- and immunohistochemical combined methods provide a precise diagnosis and confirm the GCT's neural origin, which has been disputed for years.
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DiBona, Gerald F. "Neural control of the kidney: functionally specific renal sympathetic nerve fibers." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 279, no. 5 (November 1, 2000): R1517—R1524. http://dx.doi.org/10.1152/ajpregu.2000.279.5.r1517.
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The sympathetic nervous system provides differentiated regulation of the functions of various organs. This differentiated regulation occurs via mechanisms that operate at multiple sites within the classic reflex arc: peripherally at the level of afferent input stimuli to various reflex pathways, centrally at the level of interconnections between various central neuron pools, and peripherally at the level of efferent fibers targeted to various effectors within the organ. In the kidney, increased renal sympathetic nerve activity regulates the functions of the intrarenal effectors: the tubules, the blood vessels, and the juxtaglomerular granular cells. This enables a physiologically appropriate coordination between the circulatory, filtration, reabsorptive, excretory, and renin secretory contributions to overall renal function. Anatomically, each of these effectors has a dual pattern of innervation consisting of a specific and selective innervation by unmyelinated slowly conducting C-type renal sympathetic nerve fibers in addition to an innervation that is shared among all the effectors. This arrangement permits the maximum flexibility in the coordination of physiologically appropriate responses of the tubules, the blood vessels, and the juxtaglomerular granular cells to a variety of homeostatic requirements.
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Kim, Myung Woo, Sun Hee Chang, and Ick Soo Choi. "Granular cell tumor that originated in a posterior ethmoid sinus." International Journal of Otorhinolaryngology and Head and Neck Surgery 3, no. 3 (June 24, 2017): 721. http://dx.doi.org/10.18203/issn.2454-5929.ijohns20173054.
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<p class="abstract"><span lang="EN-US">A granular cell tumor (GCT) is a rare neoplasm. It grows slowly, presumably originates from a Schwann cell, and is typically benign. Histopathologically, GCTs are composed of loosely infiltrating sheets of large, pale, polyhedral cells with abundant granular eosinophilic cytoplasm and a pale, centrally situated nucleus. Immunohistochemically, GCTs express the S-100 protein and neuron-specific enolase. A GCT can occur anywhere in the body. Half of all GCTs occur in the head and neck regions, especially on the tongue, but they are rarely found in the nasal cavity. A GCT usually arises as a solitary tumor and can be confirmed only by a histologic examination. The appropriate treatment is excision of the lesion. </span>Here, we present a rare case of a GCT originating in the right posterior ethmoid sinus in the nasal cavity. A GCT originating in a posterior ethmoid sinus has not been reported thus far. In our case, a simple nasal polyp was found in the left ethmoid sinus of the patient. Thus, we initially misjudged the GCT in the right nasal cavity as a simple nasal polyp.</p>
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Idzhilova, O. S., N. A. Simonova, M. G. Minlebaev, and A. Yu Malyshev. "Infragranular excitatory projection to granular neurons in neonatal rodent somatosensory neocortex." Genes & Cells 18, no. 4 (December 15, 2023): 771–73. http://dx.doi.org/10.17816/gc623337.
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Though the principles of central nervous system development are genetically encoded, the cortical activity is also critically involved in these processes. While this question is quite important, up to now we are limited in our understanding of the role that neuronal activity plays in formation of functionally linked cellular ensembles in the developing cortex. Recently, transient inhibitory neuronal projections were shown in the barrel cortex during the critical period of its development. Expression of interneuronal connections from infragranular to other cortical layers exactly during the period of barrel formation suggests their critical role in establishment of adult-like columnar organization of the barrel cortex. While the inhibitory connections were demonstrated, the question remains, whether the transient connectivity is restricted by emergence of inhibitory projections, or both types (including excitatory connections) could be expressed during the critical period of the barrel cortex development. Here, we aimed to answer this question using in vitro optogenetic stimulation of the neurons in the infragranular layers of the neonatal mouse barrel cortex. A viral vector of serotype AAV.PHP.eB containing channelrhodopsin-2 along with a fluorescent Venus tag sequence under the hSyn promoter was delivered via intraventricular injection into the neonatal mouse brain at P0. This transduction protocol resulted in neuron-specific expression of the construct primarily in the L2/3, L5 and L6 cortical layers at P7. At P7, acute coronal brain slices containing the barrel cortical field were prepared. For a given cortical column, the infragranular layers were optogenetically mapped while simultaneous whole-cell electrophysiological registration of a pyramidal cell in the barrel was performed. Holding potential was varied to discriminate between light-evoked EPSCs and IPSCs. The results of our preliminary recordings in the neonatal somatosensory cortex showed presence of neuronal projections from infra- to granular layer, which is in agreement with the already demonstrated data. However, L4 EPSCs evoked by infragranular layer stimulation were also recorded, suggesting the expression of the excitatory connections from infra- to granular layers early in development. Though we require to continue our recordings, our findings suggest an even more complex network interactions that shape the barrel cortex L4 during the early postnatal stages.
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Schofield, Geoffrey G., Henry L. Puhl, and Stephen R. Ikeda. "Properties of Wild-Type and Fluorescent Protein-Tagged Mouse Tetrodotoxin-Resistant Sodium Channel (NaV1.8) Heterologously Expressed in Rat Sympathetic Neurons." Journal of Neurophysiology 99, no. 4 (April 2008): 1917–27. http://dx.doi.org/10.1152/jn.01170.2007.
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The tetrodotoxin (TTX)-resistant Na+ current arising from NaV1.8-containing channels participates in nociceptive pathways but is difficult to functionally express in traditional heterologous systems. Here, we show that injection of cDNA encoding mouse NaV1.8 into the nuclei of rat superior cervical ganglion (SCG) neurons results in TTX-resistant Na+ currents with amplitudes equal to or exceeding the currents arising from natively expressing channels of mouse dorsal root ganglion (DRG) neurons. The activation and inactivation properties of the heterologously expressed NaV1.8 Na+ channels were similar but not identical to native TTX-resistant channels. Most notably, the half-activation potential of the heterologously expressed NaV1.8 channels was shifted about 10 mV toward more depolarized potentials. Fusion of fluorescent proteins to the N- or C-termini of NaV1.8 did not substantially affect functional expression in SCG neurons. Unexpectedly, fluorescence was not concentrated at the plasma membrane but found throughout the interior of the neuron in a granular pattern. A similar expression pattern was observed in nodose ganglion neurons expressing the tagged channels. In contrast, expression of tagged NaV1.8 in HeLa cells revealed a fluorescence pattern consistent with sequestration in the endoplasmic reticulum, thus providing a basis for poor functional expression in clonal cell lines. Our results establish SCG neurons as a favorable surrogate for the expression and study of molecularly defined NaV1.8-containing channels. The data also indicate that unidentified factors may be required for the efficient functional expression of NaV1.8 with a biophysical phenotype identical to that found in sensory neurons.
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Nixima, Ken'ichi, Kazuo Okanoya, Noritaka Ichinohe, and Tohru Kurotani. "Fast voltage-sensitive dye imaging of excitatory and inhibitory synaptic transmission in the rat granular retrosplenial cortex." Journal of Neurophysiology 118, no. 3 (September 1, 2017): 1784–99. http://dx.doi.org/10.1152/jn.00734.2016.
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Rodent granular retrosplenial cortex (GRS) has dense connections between the anterior thalamic nuclei (ATN) and hippocampal formation. GRS superficial pyramidal neurons exhibit distinctive late spiking (LS) firing property and form patchy clusters with prominent apical dendritic bundles. The aim of this study was to investigate spatiotemporal dynamics of signal transduction in the GRS induced by ATN afferent stimulation by using fast voltage-sensitive dye imaging in rat brain slices. In coronal slices, layer 1a stimulation, which presumably activated thalamic fibers, evoked propagation of excitatory synaptic signals from layers 2–4 to layers 5–6 in a direction perpendicular to the layer axis, followed by transverse signal propagation within each layer. In the presence of ionotropic glutamate receptor antagonists, inhibitory responses were observed in superficial layers, induced by direct activation of inhibitory interneurons in layer 1. In horizontal slices, excitatory signals in deep layers propagated transversely mainly from posterior to anterior via superficial layers. Cortical inhibitory responses upon layer 1a stimulation in horizontal slices were weaker than those in the coronal slices. Observed differences between coronal and horizontal planes suggest anisotropy of the intracortical circuitry. In conclusion, ATN inputs are processed differently in coronal and horizontal planes of the GRS and then conveyed to other cortical areas. In both planes, GRS superficial layers play an important role in signal propagation, which suggests that superficial neuronal cascade is crucial in the integration of multiple information sources. NEW & NOTEWORTHY Superficial neurons in the rat granular retrosplenial cortex (GRS) show distinctive late-spiking (LS) firing property. However, little is known about spatiotemporal dynamics of signal transduction in the GRS. We demonstrated LS neuron network relaying thalamic inputs to deep layers and anisotropic distribution of inhibition between coronal and horizontal planes. Since deep layers of the GRS receive inputs from the subiculum, GRS circuits may work as an integrator of multiple sources such as sensory and memory information.
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Kaplan, R., A. Burgos, N. Rodríguez, Z. Meza Vetanzo, S. Ortiz, and D. J. Piccinni. "Paraganglioma pulmonar primario como tumor incidental." Revista de la Facultad de Ciencias Médicas de Córdoba 67, no. 3 (September 10, 2010): 118–22. http://dx.doi.org/10.31053/1853.0605.v67.n3.22633.
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Primary lung paragangliomas are rare. They are 1-2% of the paragangliomas, and most of them occur in patients of 43-61 years. They clinically appear as solitary tumors and are in general asymptomatic. These tumors show a nesting pattern (Zellballen) of chief polygonal cells locked by fibrovascular trabeculae with subtenticular cells. The main cells have uniform nuclei with granular eosinophilic cytoplasm, and they are positive for neuroendocrinal markers (Neuron Specific Enolase, sinaptofisine and cromogranine A). Sustentacular cells are positive for protein S-100 and neurofibrilar protein. A differential diagnosis with the carcinoid tumor can be very difficult. The surgical treatment is mandatory , specially high blood pressure and the chances of malignization.
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Flace, P., V. Benagiano, L. Lorusso, F. Girolamo, A. Rizzi, D. Virgintino, L. Roncali, and G. Ambrosi. "Glutamic acid decarboxylase immunoreactive large neuron types in the granular layer of the human cerebellar cortex." Anatomy and Embryology 208, no. 1 (April 1, 2004): 55–64. http://dx.doi.org/10.1007/s00429-003-0374-x.
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Chuong, C. M., K. L. Crossin, and G. M. Edelman. "Sequential expression and differential function of multiple adhesion molecules during the formation of cerebellar cortical layers." Journal of Cell Biology 104, no. 2 (February 1, 1987): 331–42. http://dx.doi.org/10.1083/jcb.104.2.331.
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We have correlated the times of appearance of the neural cell adhesion molecule (N-CAM), the neuron-glia cell adhesion molecule (Ng-CAM), and the extracellular matrix protein, cytotactin, during the development of the chicken cerebellar cortex, and have shown that these molecules make different functional contributions to granule cell migration. Immunofluorescent staining showed distinct spatiotemporal expression sequences for each adhesion molecule. N-CAM was present at all times in all layers. However, the large cytoplasmic domain polypeptide of N-CAM was always absent from the external granular layer and was enriched in the molecular layer as development proceeded. Ng-CAM began to be expressed in the premigratory granule cells just before migration and later disappeared from cell bodies but remained on parallel fibers. Cytotactin, which is synthesized by glia and not by neurons, appeared first in a speckled pattern within the external granular layer and later appeared in a continuous pattern along the Bergmann glia; it was also enriched in the molecular layer. After we established their order of appearance, we tested the separate functions of these adhesion molecules in granule cell migration by adding specific antibodies against each molecule to cerebellar explant cultures that had been labeled with tritiated thymidine and then measuring the differential distribution of labeled cells in the forming layers. Anti-N-CAM showed marginal effects. In contrast, anti-Ng-CAM arrested most cells in the external granular layer, while anti-cytotactin arrested most cells in the molecular layer. Time course analyses combined with sequential addition of different antibodies in different orders showed that anti-Ng-CAM had a major effect in the early period (first 36 h in culture) and a lesser effect in the second part of the culture period, while anti-cytotactin had essentially no effect at the earlier time but had major effects at a later period (18-72 h in culture). The two major stages of cerebellar granule cell migration thus appear to be differentially affected by distinct adhesion molecules of different cellular origins, binding mechanisms, and overall distributions. The results indicated that local cell surface modulation of adhesion molecules of different specificities at defined stages and sites is essential to the formation of cerebellar cortical layers.
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van Kann, Elisabeth, Bruno Cozzi, Patrick R. Hof, and Helmut H. A. Oelschläger. "Qualitative and Quantitative Analysis of Primary Neocortical Areas in Selected Mammals." Brain, Behavior and Evolution 90, no. 3 (2017): 193–210. http://dx.doi.org/10.1159/000477431.
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The present study focuses on the relationship between neocortical structures and functional aspects in three selected mammalian species. Our aim was to compare cortical layering and neuron density in the projection areas (somatomotor, M1; somatosensory, S1; auditory, A1; and visual, V1; each in a wider sense). Morphological and design-based stereological analysis was performed in the wild boar (Sus scrofa scrofa) as a representative terrestrial hoofed animal (artiodactyl) and the common dolphin (Delphinus delphis) as a highly derived related aquatic mammal (cetartiodactyl). For comparison, we included the human (Homo sapiens) as a well-documented anthropoid primate. In the cortex of many mammals, layer IV (inner granular layer) is the main target of specific thalamocortical inputs while layers III and V are the main origins of neocortical projections. Because the fourth layer is indistinct or mostly lacking in the primary neocortex of the wild boar and dolphins, respectively, we analyzed the adjacent layers III and V in these animals. In the human, all the three layers were investigated separately. The stereological data show comparatively low neuron densities in all areas of the wild boar and high cell counts in the human (as expected), particularly in the primary visual cortex. The common dolphin, in general, holds an intermediate position in terms of neuron density but exhibits higher values than the human in a few layers. With respect to the situation in the wild boar, stereological neuron counts in the dolphin are consistently higher, with a maximum in layer III of the visual cortex. The extended auditory neocortical field in dolphins and the hypertrophic auditory pathway indicate secondary neurobiological adaptations to their aquatic habitat during evolution. The wild boar, however, an omnivorous quadruped terrestrial mammal, shows striking specializations as to the sensorimotor neurobiology of the snout region.
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Patnaik, A. K. "Histologic and Immunohistochemical Studies of Granular Cell Tumors in Seven Dogs, Three Cats, One Horse, and One Bird." Veterinary Pathology 30, no. 2 (March 1993): 176–85. http://dx.doi.org/10.1177/030098589303000211.
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In a retrospective study, granular cell tumors in six dogs (Nos. 1–6), three cats (Nos. 1–3), one horse (No. 1), and one cockatiel ( Nymphicus hollandicus) (No. 1) and a meningioma with a granular cell component in one dog (No. 7) were examined histologically and immunohistochemically. These tumors were identified by histologic examination of surgical biopsy specimens, except in the horse, in which the tumor was an incidental finding at necropsy. These diagnoses were initially made by more than one pathologist. Five of the six granular cell tumors in the dogs were in the oral cavity; one of these was in the maxillary gingiva of a 6-month-old puppy. The tumors in the cats were located in the tongue, vulva, and digit. The tumor in the horse was in the lung, and the tumor in the cockatiel was in the periocular tissue. Histologically, all granular cell tumors were characterized by oval to polygonal cells of various sizes. The cells had abundant, pale, eosinophilic cytoplasm with distinct intracytoplasmic granules, distinct cell margins, and mostly central nuclei. In the dogs, the gingival tumor had a large amount of collagen tissue, the tumor in the tongue had dilated blood vessels, and the maxillary tumor in the puppy was more cellular than the other tumors. The tumors in the cats were more anaplastic than the other tumors; one, located in the digit, was considered malignant. The granules in all of the tumors stained with periodic acid-Schiff and were diastase resistant. On staining with Luxol fast blue, the granules of all tumors stained different shades of pink, with the exception of the tumor in the tongue of a cat, which stained bluish green. Immunocytochemically, all tumors except the tumor in the cockatiel reacted against antibodies to vimentin. The granular cell tumor in the lung of the horse and the intracranial meningioma in a dog reacted to the antibody S-100 protein; the tumor in the horse reacted to neuron-specific enolase; tumors in two dogs (gingiva and skin) reacted to L-antitrypsin, and the maxillary tumor also reacted to lysozyme; the malignant tumor in the digit of a cat and the periocular tumor in the cockatiel reacted to muscle common actin and actin; the tumor in the cockatiel also reacted to desmin. Results of these immunocytochemical studies suggest that granular cell tumors, like tumors composed of rhabdoid cells, clear cells, and oncocytes, can have similar morphologic features but be of different cellular origins.
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Mori, Osamu, Hiroshi Hachisuka, Fumino Sakamoto, Hirofumi Nomura, and Yoichiro Sasai. "Immunohistochemical observation of S-100 protein and neuron specific enolase in the tumour cells of granular cell tumour." Acta Histochemica 83, no. 1 (January 1988): 33–38. http://dx.doi.org/10.1016/s0065-1281(88)80068-0.
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Welle, Cristin G., and Diego Contreras. "Sensory-driven and spontaneous gamma oscillations engage distinct cortical circuitry." Journal of Neurophysiology 115, no. 4 (April 1, 2016): 1821–35. http://dx.doi.org/10.1152/jn.00137.2015.
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Gamma oscillations are a robust component of sensory responses but are also part of the background spontaneous activity of the brain. To determine whether the properties of gamma oscillations in cortex are specific to their mechanism of generation, we compared in mouse visual cortex in vivo the laminar geometry and single-neuron rhythmicity of oscillations produced during sensory representation with those occurring spontaneously in the absence of stimulation. In mouse visual cortex under anesthesia (isoflurane and xylazine), visual stimulation triggered oscillations mainly between 20 and 50 Hz, which, because of their similar functional significance to gamma oscillations in higher mammals, we define here as gamma range. Sensory representation in visual cortex specifically increased gamma oscillation amplitude in the supragranular (L2/3) and granular (L4) layers and strongly entrained putative excitatory and inhibitory neurons in infragranular layers, while spontaneous gamma oscillations were distributed evenly through the cortical depth and primarily entrained putative inhibitory neurons in the infragranular (L5/6) cortical layers. The difference in laminar distribution of gamma oscillations during the two different conditions may result from differences in the source of excitatory input to the cortex. In addition, modulation of superficial gamma oscillation amplitude did not result in a corresponding change in deep-layer oscillations, suggesting that superficial and deep layers of cortex may utilize independent but related networks for gamma generation. These results demonstrate that stimulus-driven gamma oscillations engage cortical circuitry in a manner distinct from spontaneous oscillations and suggest multiple networks for the generation of gamma oscillations in cortex.
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KATO, Masumi, Yasuo WATANABE, Satoshi IINO, Yuri TAKAOKA, Shigeru KOBAYASHI, Tatsuya HAGA, and Hiroyoshi HIDAKA. "Cloning and expression of a cDNA encoding a new neurocalcin isoform (neurocalcin α) from bovine brain." Biochemical Journal 331, no. 3 (May 1, 1998): 871–76. http://dx.doi.org/10.1042/bj3310871.
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Neurocalcin (NC), a neuron-specific EF-hand Ca2+-binding protein, purified from bovine brain [Terasawa, Nakano, Kobayashi and Hidaka (1992) J. Biol. Chem. 267, 19596–19599] contains multiple isoforms. We previously cloned NCδ from bovine brain and showed high expression in neuronal tissues [Okazaki, Watanabe, Ando, Hagiwara, Terasawa and Hidaka (1992) Biochem. Biophys. Res. Commun. 185, 147–153]. We report here the molecular cloning and expression of a cDNA encoding bovine brain NCα. The translated bovine protein is 191 amino acids long and shares 69.1% of its amino acid sequence with NCδ. Recombinant NCα migrates as a single 23 kDa band and exhibits a Ca2+-dependent mobility shift on SDS/PAGE. Analysis of fluorescence emission spectra showed the Ca2+-induced peak at 337 nm. Interestingly, the mobility shift and the fluorescence intensity at 337 nm were larger for NCα than for NCδ. In Ca2+-overlay experiments, however, the apparent affinity of NCα for 45Ca2+ was similar to that of NCδ. Immunohistochemical analysis revealed NCα expression in the granular layer of the rat cerebellar cortex whereas NCδ was found in the Purkinje cell layer. In the rat olfactory bulb, NCα was located in external tufted cells, and NCδ was found in the periglomerular cells. These data demonstrate that NC isoforms differ in their tissue distribution and conformational changes induced by Ca2+ binding. Thus differential regulation of the two NC isoforms may be involved in control of neuron function.
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Marakhouski, Kirill, Andrei Zapalianski, Denis Ovseichik, Katsiaryna Nikalayeva, Aleh Pataleta, Liubou Nestsiaruk, and Hanna Kudlasevich. "Rare clinical case: granular cell tumor of the esophagus (Aprikosov tumor) in a teenager." Paediatric Surgery. Ukraine, no. 4(73) (December 30, 2021): 77–83. http://dx.doi.org/10.15574/ps.2021.73.77.
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Granular cell tumors were first described by Weber in 1854. But its muscular origin was suggested, studied in detail and differentiated by the pathologist A.I. Abrikosov in 1926. With the development of immunohistochemical analysis, a version of Abrikosov's tumor pathogenesis appeared, suggesting its origin from Schwann cells. The data obtained confirmed the presence of protein S-100, neuron-specific enolase (NSE) and CD68 in tumor cells. At present, when carrying out histochemical analysis, the expression of proteins S-100 and CD68 in tumor cells is a diagnostic criterion for Abrikosov's tumor. In treatment of granular cell tumors of the esophagus, preference is given to minimally invasive endoscopic techniques, since conservative therapy has proved to be ineffective. Considering that in most cases the tumor is benign in nature, recently many authors have recommended endoscopic resection of the mucous membrane and dissection in the submucosa. This article presents the experience of treating a child with a rare Abrikosov's tumor in the lower third of the esophagus using endoscopic technique. The clinical case described proved to be a difficult diagnostic task, since Abrikosov's tumor in the esophagus in a teenager is an extremely rare pathology with a rare localization. To remove the tumor, a non-standard endoscopic technique was chosen, which made it possible to remove the formation in a single block, that is, radically, since preoperative morphological verification was impossible. Much attention is focused on the importance of endoscopic examination in diagnostic screening and the choice of treatment tactics. This work demonstrates high efficiency and safety of endoscopic tumor removal in this localization. The use of this surgical treatment technique made it possible to radically remove the tumor and ensure a smooth course of the postoperative period. The research was carried out in accordance with the principles of the Helsinki declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: granular cell tumor, Abrikosov's tumor, tumor of the esophagus, esophagus, children, endoscopic treatment.
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Lee, Sora, Hyun-Ji Choi, Han-Byul Lee, Sung-Min Jo, Ji-hye Mun, and Woo-Chan Son. "Renal oncocytoma in a cat with chronic renal failure." Journal of Feline Medicine and Surgery Open Reports 3, no. 1 (January 2017): 205511691769349. http://dx.doi.org/10.1177/2055116917693491.
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Case summary A 9-year-old male neutered domestic shorthair cat presented with anorexia. Ultrasonography showed an irregularly shaped hypoechoic mass in the cranial pole of the right kidney. Ultrasound-guided fine-needle aspiration of the renal mass was performed. Cytology revealed moderate cellularity smears composed of epithelial cell clusters, which consisted of an exclusive population of oncocytic cells seen in sheets and papillary clusters along with abundant single cells. A moderate-to-abundant amount of densely stained granular cytoplasm with round nuclei and indistinct nucleoli was seen. The cytological diagnosis was renal oncocytic neoplasm. CT and surgical resection revealed a firm tan mass in the right kidney. A final diagnosis of renal oncocytoma was made on the basis of histology, immunohistochemical staining profile (positive for cytokeratin, and negative for chromogranin A, neuron-specific enolase and vimentin) of neoplastic cells, together with the electronic microscopy results. Relevance and novel information We believe that this is the first report of the cytological features of feline renal oncocytoma.
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Varyani, Neeraj, Anubhav Thukral, Sunny Garg, Kailash Kumar Gupta, Ravi Tandon, and Kamlakar Tripathi. "Atypical Neurofibroma and Osteosclerotic Metastasis." Case Reports in Oncological Medicine 2012 (2012): 1–4. http://dx.doi.org/10.1155/2012/301437.
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35-year-old male presented with multiple swellings in left leg, headache, weakness of limbs for 4 months, and blurring of vision for the last 15 days. On examination, he was pale, cachexic with generalized lymphadenopathy and lower motor neuron type weakness of limbs sparing right upper limb. Blood investigations showed anemia with high alkaline phosphatase. Chest radiograph revealed osteosclerotic metastatic lesion in humerus. Biopsy of leg lesion revealed atypical neurofibroma. Computed tomography (CT) of thorax revealed osteoblastic metastasis. Bone marrow aspiration showed cells with round to oval nuclei, fine granular chromatin with large central prominent nucleoli and eosinophilic cytoplasm with acini formation. Magnetic resonance imaging (MRI) of brain and spinal cord defined metastatic leptomeningeal deposits. Cerebrospinal fluid (CSF) cytology was positive for malignant cells. Gastroscopy showed an ulceroinfiltrative growth from stomach which on histopathology revealed diffuse adenocarcinoma. Palliative treatment was given with intrathecal methotrexate and systemic corticosteroid with chemotherapy. Patient’s symptom improved drastically, but we lost him to followup.
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Crump, Ryan, Kathryn Saatman, Anthony DeSana, and Binoy Joseph. "Insulin‐like Growth Factor‐1 Treatment of Experimental Traumatic Brain Injury Increases Newborn Neuron Migration Through the Granular Cell Layer." FASEB Journal 34, S1 (April 2020): 1. http://dx.doi.org/10.1096/fasebj.2020.34.s1.05804.
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Kuwamura, M., J. Yamate, T. Kotani, T. Takeuchi, and S. Sakuma. "Canine Peripheral Nerve Sheath Tumor with Eosinophilic Cytoplasmic Globules." Veterinary Pathology 35, no. 3 (May 1998): 223–26. http://dx.doi.org/10.1177/030098589803500309.
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A 13-year-old male Shetland Sheepdog had a subcutaneous tumor in the left brachium. The tumor was removed and recurred several times at 5, 13, 16, 22, and 31 months after the initial presentation. Histologically, the removed nodules from the fourth resection were composed of neoplastic proliferation of round to fusiform cells, which possessed eosinophilic globules in their cytoplasm. The globules were periodic acid–Schiff positive and diastase resistant. Positive reactions for acid phosphatase were observed in the cytoplasm of the tumor cells. Ultrastructurally, these globules consisted of membrane-bound, dense structures containing dense granules, lucent vacuoles, and homogeneous materials. The recurrent tumors removed at the fifth resection consisted of spindle cell proliferation arranged in interlacing fascicles with wavy nuclei and containing a small number of cells with cytoplasmic globules. The tumor cells were immunoreactive to vimentin, S-100 protein, myelin basic protein, and neuron-specific enolase. The tumor was diagnosed as a peripheral nerve sheath tumor with eosinophilic cytoplasmic globules. These findings are unique for the histogenesis of granular cell tumors.
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Letić-Gavrilović, A., and K. Abe. "Localization of Chromogranins, Non-neuron-specific Enolase, and Different Forms of Somatostatins in the Submandibular Salivary Glands of Mice." Journal of Dental Research 69, no. 8 (August 1990): 1494–99. http://dx.doi.org/10.1177/00220345900690080901.
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The localizations of chromogranins A, B, and C, neuron-specific enolase (NSE, γγ-type) and non-NSE (αα-type), and different forms of somatostatins were immunocytochemically identified. The localizations were compared with those of epidermal growth factor (EGF) and nerve growth factor (NGF) in the submandibular salivary glands (SMG) of male mice at five to six weeks of age, with use of a variety of antibodies and the peroxidase-antiperoxidase (PAP) and avidin-biotin complex (ABC) detection methods. In the SMG of male mice, the major chromogranin present was chromogranin A, whereas chromogranins B and C were not detected at these ages by either method. Chromogranin Alike immunoreactivity was located in the granular convoluted tubule (GCT) cells of the SMG, whereas non-NSE immunoreactivity was observed throughout the duct system and in some acinar-associated cells. NSE was not detected in any part of the SMG. The distribution of chromogranin A and somatostatins in the GCT cells was similar to that of EGF and NGF. Our results strongly suggest that chromogranin A and somatostatins, but not chromogranin B or C, may be useful as a means of differentiation of the cells in the duct system of the SMG responsible for the production of biologically-active factors.
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Vlasenko, O. V., I. V. Gunas, A. I. Semenenko, A. V. Dovgan, and V. P. Bobruk. "Morphogenesis of the human brain and cerebellum in the early prenatal period." Reports of Vinnytsia National Medical University 27, no. 2 (May 29, 2023): 204–8. http://dx.doi.org/10.31393/reports-vnmedical-2023-27(2)-04.
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Annotation. Neurogenesis is a complex process of neuron formation that is central to the formation of most neurons in the human brain during vertebrate development. The purpose of this study was to establish and compare the parameters of the cerebellum and the endbrain of humans at 8-9 weeks of intrauterine development, as well as the features of cytoarchitectonics, which is inherent in the studied period of gestation. In the process of scientific research, 10 fetuses of 8-9 weeks were examined and research methods were applied, such as: immunohistochemical, anatomical-histological and morphometric. The morphometric study was carried out using a light microscope MBS-10 and SIGETA. Studies were performed at magnifications of ×4, ×10, ×20, ×40, and ×100. From the obtained histological sections, photofixation and morphometry were performed using the ETREK Ucmos camera and the ToupViem computer program (computer histometry). Statistical processing of digital data was applied using the software package “Statistica 6.0” from Statsoft (license number BXXR901E246122FA). During the study, we observed that the total thickness of the studied area varied depending on the part of the endbrain. In the hemispheres of the endbrain of 8-9 week fetuses, the presence of such layers as ventricular, subventricular, intermediate and cortical was noted, whereas examining the cerebellum, we witnessed the presence of the ventricular zone, intermediate, molecular and external granular zone. The expression of proliferated neural stem cells in the layers of the endbrain was the most active in the ventricular zone, compared to the others. Migration of neural stem cells in the cerebellum, in the ventricular and external granular zones occurs in two directions: tangential and radial. Weak expression of synaptophysin is observed in the cerebellum. In the endbrain, synaptophysin expression was strong in the intermediate and cortical zones. Fibers of radial glia of an 8-9 week fetus penetrate all zones of the endbrain and cerebellum. On a horizontal histological section of the terminal brain of human fetuses, the cavities of the ventricles were visualized and the development of vascular plexuses in the lateral ventricles of the brain was noted. Thus, in the course of the research, we compared the features of cytoarchitectonics, morphometric parameters of the structures of the endbrain and cerebellum of human fetuses of 8-9 weeks of intrauterine development.
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Sakanaka, M., S. Magari, T. Shibasaki, K. Shinoda, and J. Kohno. "A reliable method combining horseradish peroxidase histochemistry with immuno-beta-galactosidase staining." Journal of Histochemistry & Cytochemistry 36, no. 9 (September 1988): 1091–96. http://dx.doi.org/10.1177/36.9.3136206.
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A sensitive combination of horseradish peroxidase (HRP) tracing and immunohistochemistry was used by Rye et al. [J Histochem Cytochem (1984) 32:1145] in a search for the origins of neurotransmitter- and neuromodulator-containing nerve fibers in brain. In this combination, peroxidase as a marker in immunohistochemistry was thought to yield a homogeneous brown immunoreaction product of diaminobenzidine, different from the black granular reaction product of retrogradely transported HRP, which is visualized by the tetramethylbenzidine (TMB) reaction and subsequent stabilization. A neuron that exhibits both kinds of reaction products in its cytoplasm in sections subjected to combination staining is referred to as a double-labeled cell. With a combined HRP and corticotropin-releasing factor (CRF) immunoperoxidase-antiperoxidase (PAP) method, the first set of experiments showed "false" double-labeled cells in the pyramidal cell layer of rat cerebral cortex, but only rarely in the subcortical areas, possibly because of the use of one enzyme system in two different histochemical procedures. This limitation of the double-staining technique prompted us to demonstrate an alternate combination of HRP tracing and immunohistochemistry in the second set of experiments by employing two previously described independent enzyme systems: HRP as a retrograde tracer and beta-galactosidase as a marker for immunohistochemical demonstration of CRF. A homogeneous blue reaction product indicated immuno-beta-galactosidase staining, and a granular black or brown reaction product labeled retrogradely transported HRP in double-labeled cells in subcortical regions. Neither double labeling nor "false" double labeling was seen in pyramidal cells of cerebral cortex. These findings suggest that application of two independent enzyme systems in a combined HRP and immunohistochemical method may be useful for investigating in origins of peptidergic fibers in brain when the combination of HRP histochemistry and the PAP method appears to be inappropriate.
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Prestori, F., P. Rossi, B. Bearzatto, J. Laine, D. Necchi, S. Diwakar, S. N. Schiffmann, H. Axelrad, and E. D'Angelo. "Altered Neuron Excitability and Synaptic Plasticity in the Cerebellar Granular Layer of Juvenile Prion Protein Knock-Out Mice with Impaired Motor Control." Journal of Neuroscience 28, no. 28 (July 9, 2008): 7091–103. http://dx.doi.org/10.1523/jneurosci.0409-08.2008.
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Fujii, Masako. "Projections to the hippocampal and cerebellar microneuron (granular neuron) areas from the olfactory bulb transplanted into the hippocampal formation and the cerebellum." Neuroscience Research Supplements 14 (January 1991): S41. http://dx.doi.org/10.1016/s0921-8696(06)80110-6.
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Koontz, Thad, Marina Bralic, Jelena Tomac, Ester Pernjak-Pugel, Glen Bantug, Stipan Jonjic, and William J. Britt. "Altered development of the brain after focal herpesvirus infection of the central nervous system." Journal of Experimental Medicine 205, no. 2 (February 11, 2008): 423–35. http://dx.doi.org/10.1084/jem.20071489.
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Human cytomegalovirus infection of the developing central nervous system (CNS) is a major cause of neurological damage in newborn infants and children. To investigate the pathogenesis of this human infection, we developed a mouse model of infection in the developing CNS. Intraperitoneal inoculation of newborn animals with murine cytomegalovirus resulted in virus replication in the liver followed by virus spread to the brain. Virus infection of the CNS was associated with the induction of inflammatory responses, including the induction of a large number of interferon-stimulated genes and histological evidence of focal encephalitis with recruitment of mononuclear cells to foci containing virus-infected cells. The morphogenesis of the cerebellum was delayed in infected animals. The defects in cerebellar development in infected animals were generalized and, although correlated temporally with virus replication and CNS inflammation, spatially unrelated to foci of virus-infected cells. Specific defects included decreased granular neuron proliferation and migration, expression of differentiation markers, and activation of neurotrophin receptors. These findings suggested that in the developing CNS, focal virus infection and induction of inflammatory responses in resident and infiltrating mononuclear cells resulted in delayed cerebellar morphogenesis.
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Kelley, L. C., M. Puette, K. A. Langheinrich, and B. King. "Bovine Pulmonary Blastomas: Histomorphologic Description and Immunohistochemistry." Veterinary Pathology 31, no. 6 (November 1994): 658–62. http://dx.doi.org/10.1177/030098589403100605.
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Three adult female dairy cattle with pulmonary blastomas were evaluated. The gross lesions at postmortem were described as multiple white circumscribed masses throughout the lungs, with pleural involvement in one cow and lymph node metastasis in the other two cows. Histologically, the tumors contained a dual population of mesenchymal and epithelial neoplastic cells. Epithelial cells formed nests, tubules, and formations resembling bronchioles of normal lung. Mesenchymal cells were spindle shaped with oval nuclei and fibrillar eosinophilic cytoplasm, were large rounded cells with multiple round nuclei and granular eosinophilic cytoplasm, or appeared blast-like, with large hyperchromatic nuclei and amphophilic cytoplasm. The tumors varied greatly in appearance from one field to another within the same tumor. Epithelial cells stained positively with anii-cytokeratin antibodies. Some spindle-shaped mesenchymal cells exhibited smooth muscle cell differentiation with positive staining with anti-vimentin, anti-muscle-specific actin, and anti-smooth muscle actin antibodies, whereas other rounded mesenchymal cells expressed striated muscle cell differentiation with multiple nuclei and positivity to anti-neuron-specific enolase and anti-muscle-specific actin antibodies. The variable expression of the intermediate filaments and cytoplasmic enzymes indicates multiple pathways of differentiation in the pulmonary blastomas.
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Rodini, Carolina Oliveira, Daniela Emi Suzuki, Adriana Miti Nakahata, Márcia Cristina Leite Pereira, Luciana Janjoppi, Silvia Regina Caminada Toledo, and Oswaldo Keith Okamoto. "Aberrant signaling pathways in medulloblastomas: a stem cell connection." Arquivos de Neuro-Psiquiatria 68, no. 6 (December 2010): 947–52. http://dx.doi.org/10.1590/s0004-282x2010000600021.
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Medulloblastoma is a highly malignant primary tumor of the central nervous system. It represents the most frequent type of solid tumor and the leading cause of death related to cancer in early childhood. Current treatment includes surgery, chemotherapy and radiotherapy which may lead to severe cognitive impairment and secondary brain tumors. New perspectives for therapeutic development have emerged with the identification of stem-like cells displaying high tumorigenic potential and increased radio- and chemo-resistance in gliomas. Under the cancer stem cell hypothesis, transformation of neural stem cells and/or granular neuron progenitors of the cerebellum are though to be involved in medulloblastoma development. Dissecting the genetic and molecular alterations associated with this process should significantly impact both basic and applied cancer research. Based on cumulative evidences in the fields of genetics and molecular biology of medulloblastomas, we discuss the possible involvement of developmental signaling pathways as critical biochemical switches determining normal neurogenesis or tumorigenesis. From the clinical viewpoint, modulation of signaling pathways such as TGFβ, regulating neural stem cell proliferation and tumor development, might be attempted as an alternative strategy for future drug development aiming at more efficient therapies and improved clinical outcome of patients with pediatric brain cancers.
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Giovanella, L., S. la Rosa, L. Ceriani, S. Uccella, P. Erba, and S. Garancini. "Chromogranin-A as a Serum Marker for Neuroendocrine Tumors: Comparison with Neuron-Specific Enolase and Correlation with Immunohistochemical Findings." International Journal of Biological Markers 14, no. 3 (July 1999): 160–66. http://dx.doi.org/10.1177/172460089901400307.
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Background Chromogranin-A (Cg-A) is a 439-amino-acid protein contained in secretory granules of neuroendocrine cells, in addition to specific hormone peptides or neuropeptides. Since Cg-A is co-released with peptide hormones its serum concentration can be used as a marker of neuroendocrine tumors. Aim Evaluation of the analytical performance of a new IRMA method for Cg-A assay and of the clinical value of serum Cg-A and neuron-specific enolase (NSE) in neuroendocrine tumors. In addition, we compared the diagnostic usefulness of both Cg-A and NSE serum levels and their relationship to tissue expression. Patients and methods Initially we evaluated the analytical performance (intra- and interassay imprecision, dilution test and detection limit) of the Cg-A RIACT method (CIS Bio-International, Gifsur-Yvette, France). We selected 50 patients affected by various histologically confirmed neuroendocrine tumors (NETs): 111In-pentetreotide scan and helical computed tomography were employed to assess tumor extent. Cg-A and NSE were measured before surgery in serum samples of patients and 50 age-matched controls by IRMA methods. After surgery immunohistochemical stains for Cg-A and NSE were performed on surgical specimens of tumor tissue. Results Cg-A levels were significantly higher (p<0.0001) in patients with NETs than in healthy controls and we found a positive correlation between serum and tissue expression (p<0.05). Serum levels of Cg-A were also related to tumor extent (p<0.05) but in some cases we observed significant elevation of serum Cg-A in small, intensely immunoreactive NETs. ROC curve analysis showed better accuracy for serum Cg-A compared to NSE in the diagnosis of NETs, while no significant relationship was found between serum expression and immunostaining for NSE. Discussion Our results confirmed the biological and clinical significance of circulating Cg-A as an expression of granular content in neuroendocrine tissues and supported the complementary usefulness of serum Cg-A in the diagnosis and evaluation of NETs together with imaging modalities.