Journal articles: 'Neuroimmune signalling'

1

Cryan, John F., and Timothy G. Dinan. "Microbiota and neuroimmune signalling—Metchnikoff to microglia." Nature Reviews Gastroenterology & Hepatology 12, no. 9 (July 28, 2015): 494–96. http://dx.doi.org/10.1038/nrgastro.2015.127.

Full text

APA, Harvard, Vancouver, ISO, and other styles

2

Chhatar, Sushanta, and Girdhari Lal. "Role of adrenergic receptor signalling in neuroimmune communication." Current Research in Immunology 2 (2021): 202–17. http://dx.doi.org/10.1016/j.crimmu.2021.11.001.

Full text

APA, Harvard, Vancouver, ISO, and other styles

3

vergnolle, n. "Neuroimmune signalling in the gut - mediators linked to disorders?" Neurogastroenterology and Motility 18, no. 7 (July 2006): 497–98. http://dx.doi.org/10.1111/j.1365-2982.2006.00805.x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

4

Lim, Jessica SY, and Peter CA Kam. "Neuroimmune mechanisms of pain: Basic science and potential therapeutic modulators." Anaesthesia and Intensive Care 48, no. 3 (February 26, 2020): 167–78. http://dx.doi.org/10.1177/0310057x20902774.

Full text

Abstract:

This narrative review aims to describe the role of peripheral and central immune responses to tissue and nerve damage in animal models, and to discuss the use of immunomodulatory agents in clinical practice and their perioperative implications. Animal models of pain have demonstrated that nerve injury activates immune signalling pathways that drive aberrant sensory processes, resulting in neuropathic and chronic pain. This response involves the innate immune system. T lymphocytes are also recruited. Glial cells surrounding the damaged nerves release cytokines and proinflammatory mediators that activate resident immune cells and recruit circulatory immune cells. Toll-like receptors on the glial cells play a crucial role in the pathogenesis of chronic pain. Animal models indicate an immune mechanism of neuropathic pain. Analgesic drugs and anaesthetic agents have varied effects on the neuroimmune interface. Evidence of a neuroimmune interaction is mainly from animal studies. Human studies are required to evaluate the clinical implications of this neuroimmune interaction.

APA, Harvard, Vancouver, ISO, and other styles

5

Spencer, Sarah J., Abdeslam Mouihate, and Quentin J. Pittman. "Neonatal neuroimmune challenge effects on adult brain derived neurotrophic factor signalling pathways." Frontiers in Neuroendocrinology 27, no. 1 (May 2006): 107–8. http://dx.doi.org/10.1016/j.yfrne.2006.03.267.

Full text

APA, Harvard, Vancouver, ISO, and other styles

6

Kosek, E., A. Finn, C. Ultenius, A. Hugo, C. Svensson, and A. S. Ahmed. "Differences in neuroimmune signalling between male and female patients suffering from knee osteoarthritis." Journal of Neuroimmunology 321 (August 2018): 49–60. http://dx.doi.org/10.1016/j.jneuroim.2018.05.009.

Full text

APA, Harvard, Vancouver, ISO, and other styles

7

García-Ovejero, Daniel, Ángel Arévalo-Martín, Beatriz Navarro-Galve, Emmanuel Pinteaux, Eduardo Molina-Holgado, and Francisco Molina-Holgado. "Neuroimmmune interactions of cannabinoids in neurogenesis: focus on interleukin-1β (IL-1β) signalling." Biochemical Society Transactions 41, no. 6 (November 20, 2013): 1577–82. http://dx.doi.org/10.1042/bst20130198.

Full text

Abstract:

Neuroimmune networks and the brain endocannabinoid system contribute to the maintenance of neurogenesis. Activation of cannabinoid receptors suppresses chronic inflammatory responses through the attenuation of pro-inflammatory mediators. Moreover, the endocannabinoid system directs cell fate specification of NSCs (neural stem cells) in the CNS (central nervous sytem). The aim of our work is to understand better the relationship between the endocannabinoid and the IL-1β (interleukin-1β) associated signalling pathways and NSC biology, in order to develop therapeutical strategies on CNS diseases that may facilitate brain repair. NSCs express functional CB1 and CB2 cannabinoid receptors, DAGLα (diacylglycerol lipase α) and the NSC markers SOX-2 and nestin. We have investigated the role of CB1 and CB2 cannabinoid receptors in the control of NSC proliferation and in the release of immunomodulators [IL-1β and IL-1Ra (IL-1 receptor antagonist)] that control NSC fate decisions. Pharmacological blockade of CB1 and/or CB2 cannabinoid receptors abolish or decrease NSC proliferation, indicating a critical role for both CB1 and CB2 receptors in the proliferation of NSC via IL-1 signalling pathways. Thus the endocannabinoid system, which has neuroprotective and immunomodulatory actions mediated by IL-1 signalling cascades in the brain, could assist the process of proliferation and differentiation of embryonic or adult NSCs, and this may be of therapeutic interest in the emerging field of brain repair.

APA, Harvard, Vancouver, ISO, and other styles

8

Du Preez, Stanley, Helene Cabanas, Donald Staines, and Sonya Marshall-Gradisnik. "Potential Implications of Mammalian Transient Receptor Potential Melastatin 7 in the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review." International Journal of Environmental Research and Public Health 18, no. 20 (October 12, 2021): 10708. http://dx.doi.org/10.3390/ijerph182010708.

Full text

Abstract:

The transient receptor potential (TRP) superfamily of ion channels is involved in the molecular mechanisms that mediate neuroimmune interactions and activities. Recent advancements in neuroimmunology have identified a role for TRP cation channels in several neuroimmune disorders including amyotropic lateral sclerosis, multiple sclerosis, and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a debilitating disorder with an obscure aetiology, hence considerable examination of its pathobiology is warranted. Dysregulation of TRP melastatin (TRPM) subfamily members and calcium signalling processes are implicated in the neurological, immunological, cardiovascular, and metabolic impairments inherent in ME/CFS. In this review, we present TRPM7 as a potential candidate in the pathomechanism of ME/CFS, as TRPM7 is increasingly recognized as a key mediator of physiological and pathophysiological mechanisms affecting neurological, immunological, cardiovascular, and metabolic processes. A focused examination of the biochemistry of TRPM7, the role of this protein in the aforementioned systems, and the potential of TRPM7 as a molecular mechanism in the pathophysiology of ME/CFS will be discussed in this review. TRPM7 is a compelling candidate to examine in the pathobiology of ME/CFS as TRPM7 fulfils several key roles in multiple organ systems, and there is a paucity of literature reporting on its role in ME/CFS.

APA, Harvard, Vancouver, ISO, and other styles

9

Kelly, J. R., G. Clarke, J. F. Cryan, and T. G. Dinan. "Dimensional thinking in psychiatry in the era of the Research Domain Criteria (RDoC)." Irish Journal of Psychological Medicine 35, no. 2 (April 5, 2017): 89–94. http://dx.doi.org/10.1017/ipm.2017.7.

Full text

Abstract:

The biological mechanisms underlying psychiatric diagnoses are not well defined. Clinical diagnosis based on categorical systems exhibit high levels of heterogeneity and co-morbidity. The Research Domain Criteria (RDoC) attempts to reconceptualize psychiatric disorders into transdiagnostic functional dimensional constructs based on neurobiological measures and observable behaviour. By understanding the underlying neurobiology and pathophysiology of the relevant processes, the RDoC aims to advance biomarker development for disease prediction and treatment response. This important evolving dimensional framework must also consider environmental factors. Emerging evidence suggests that gut microbes (microbiome) play a physiological role in brain diseases by modulating neuroimmune, neuroendocrine and neural signalling pathways between the gut and the brain. The integration of the gut microbiome signature as an additional dimensional component of the RDoC may enhance precision psychiatry.

APA, Harvard, Vancouver, ISO, and other styles

10

Benallegue, Nail, Hania Kebir, Richa Kapoor, Alexis Crockett, Cen Li, Lara Cheslow, Mohamed S. Abdel-Hakeem, et al. "The hedgehog pathway suppresses neuropathogenesis in CD4 T cell-driven inflammation." Brain 144, no. 6 (March 16, 2021): 1670–83. http://dx.doi.org/10.1093/brain/awab083.

Full text

Abstract:

Abstract The concerted actions of the CNS and the immune system are essential to coordinating the outcome of neuroinflammatory responses. Yet, the precise mechanisms involved in this crosstalk and their contribution to the pathophysiology of neuroinflammatory diseases largely elude us. Here, we show that the CNS-endogenous hedgehog pathway, a signal triggered as part of the host response during the inflammatory phase of multiple sclerosis and experimental autoimmune encephalomyelitis, attenuates the pathogenicity of human and mouse effector CD4 T cells by regulating their production of inflammatory cytokines. Using a murine genetic model, in which the hedgehog signalling is compromised in CD4 T cells, we show that the hedgehog pathway acts on CD4 T cells to suppress the pathogenic hallmarks of autoimmune neuroinflammation, including demyelination and axonal damage, and thus mitigates the development of experimental autoimmune encephalomyelitis. Impairment of hedgehog signalling in CD4 T cells exacerbates brain-brainstem-cerebellum inflammation and leads to the development of atypical disease. Moreover, we present evidence that hedgehog signalling regulates the pathogenic profile of CD4 T cells by limiting their production of the inflammatory cytokines granulocyte-macrophage colony-stimulating factor and interferon-γ and by antagonizing their inflammatory program at the transcriptome level. Likewise, hedgehog signalling attenuates the inflammatory phenotype of human CD4 memory T cells. From a therapeutic point of view, our study underlines the potential of harnessing the hedgehog pathway to counteract ongoing excessive CNS inflammation, as systemic administration of a hedgehog agonist after disease onset effectively halts disease progression and significantly reduces neuroinflammation and the underlying neuropathology. We thus unveil a previously unrecognized role for the hedgehog pathway in regulating pathogenic inflammation within the CNS and propose to exploit its ability to modulate this neuroimmune network as a strategy to limit the progression of ongoing neuroinflammation.

APA, Harvard, Vancouver, ISO, and other styles

11

Ribeiro, Deidiane E., Heidi K. Müller, Betina Elfving, Amanda Eskelund, Samia RL Joca, and Gregers Wegener. "Antidepressant-like effect induced by P2X7 receptor blockade in FSL rats is associated with BDNF signalling activation." Journal of Psychopharmacology 33, no. 11 (September 17, 2019): 1436–46. http://dx.doi.org/10.1177/0269881119872173.

Full text

Abstract:

Background: P2X7 receptors (P2X7R) are ligand-gated ion channels activated by adenosine 5’-triphosphate (ATP), which are involved in processes that are dysfunctional in stress response and depression, such as neurotransmitter release, and neuroimmune response. Genetic and pharmacological inhibition of the P2X7R induce antidepressant-like effects in animals exposed to stress. However, the effect of P2X7R antagonism in an animal model of depression based on selective breeding has not previously been studied, and the mechanism underling the antidepressant-like effect induced by the P2X7R blockade remains unknown. Aims: The present study aimed to: (1) determine whether P2X7R blockade induces antidepressant-like effects in the Flinders Sensitive Line (FSL) rats and, (2) investigate whether brain-derived neurotrophic factor (BDNF) signalling in the frontal cortex and hippocampus is involved in this effect. Methods: FSL and the control Flinders Resistant Line (FRL) rats were treated with vehicle or the P2X7R antagonist A-804598 (3, 10 or 30 mg/Kg/day) for 1 or 7 days before being exposed to the forced swim test (FST). After the behavioural test, animals were decapitated, their brains were removed and the frontal cortex, ventral and dorsal hippocampus were dissected for BDNF signalling analysis. Results: We found that repeated treatment with A-804598 (30 mg/Kg) reduced the immobility time in the FST and activated the BDNF signalling in the ventral hippocampus of FSL rats. Conclusions: P2X7R blockade induces an antidepressant-like effect associated with increased levels of BDNF-AKT-p70 S6 kinase in the ventral hippocampus, which may be mediated by tropomyosin-related kinase B (TRKB) receptor activation supporting the notion of P2X7R antagonism as a potential new antidepressant strategy.

APA, Harvard, Vancouver, ISO, and other styles

12

Watts, Timothy John. "The Pathogenesis of Autism." Clinical medicine. Pathology 1 (January 2008): CPath.S1143. http://dx.doi.org/10.4137/cpath.s1143.

Full text

Abstract:

Autism is well known as a complex developmental disorder with a seemingly confusing and uncertain pathogenesis. The definitive mechanisms that promote autism are poorly understood and mostly unknown, yet available theories do appear to focus on the disruption of normal cerebral development and its subsequent implications on the functional brain unit. This mini-review aims solely to discuss and evaluate the most prominent current theories regarding the pathogenesis of autism. The main conclusion is that although there is not a clear pathway of mechanisms directed towards a simple pathogenesis and an established link to autism on the symptomatic level; there are however several important theories (neural connectivity, neural migration, excitatory-inhibitory neural activity, dendritic morphology, neuroimmune; calcium signalling and mirror neurone) which appear to offer an explanation to how autism develops. It seems probable that autism's neurodevelopmental defect is ‘multi-domain’ in origin (rather than a single anomaly) and is hence distributed across numerous levels of study (genetic, immunopathogenic, etc.). A more definitive understanding of the pathogenesis could facilitate the development of better treatments for this complex psychiatric disorder.

APA, Harvard, Vancouver, ISO, and other styles

13

Callejas Pina, B. E., A. Wang, S. Hamed, and D. M. Mckay. "A60 THE NEURAL SIGNAL, CALCITONIN GENE-RELATED PEPTIDE (CGRG) ENHANCES A REGULATORY PHENOTYPE IN THE HUMAN IL-4 TREATED HUMAN MACROPHAGE." Journal of the Canadian Association of Gastroenterology 5, Supplement_1 (February 21, 2022): 69–70. http://dx.doi.org/10.1093/jcag/gwab049.059.

Full text

Abstract:

Abstract Background Recent studies in pre-clinical models of disease have revealed the ability of murine and human IL-4-treated macrophages (M(IL4)) to promote wound recovery and reduce the severity of colitis. An unbiased RNA-sequence analysis of human blood-derived macrophages revealed increased expression of the RAMP1 chain of the CGRP receptor in IL-4 treated cells, raising the intriguing possibility of neural control of regulatory macrophages in the context of neuroimmune interaction in colitis. Thus, we sought to address if this mRNA signal translated into increased RAMP1 protein, if/how CGPR affected M(IL4) function, and if this applied to macrophages from patients with IBD as well as those from healthy donors. Aims To determine if CRGP-RAMP1 signalling in human IL-4 treated macrophages enhances a regulatory phenotype. Methods Peripheral blood mononuclear cells from healthy volunteers and individuals with IBD were cultured on plastic (2h, 37°C) and non-adherent cells removed. The adherent cells were cultured with recombinant hM-CSF (10 ng/ml) for 7 days. The resultant macrophages (2.5×105) were differentiated with IL-4 (48h 20 ng/mL) and assessed by qPCR and immunocytochemistry. In other cells, CGRP (10 nM) was added 24h after IL-4 and (1) cAMP (2) cytokines and (3) phagocytosis of inert FITC-beads measured, and (4) the capacity of supernatant from the cells to promote healing in wounded Caco2 epithelial monolayers tested. Results Compared to non-treated macrophages (M(0)), M(IL4)s from healthy individuals had increased mRNA for both chains of the CGRP-receptor (i.e. RAMP1 and CLR), and increased surface expression of the receptor as shown by immunostaining and CGRP-evoked cAMP. The IL-4 evoked RAMP1 mRNA was only detected in macrophages from 50% of the patients with active IBD. M(IL4)s treated with CGRP showed enhanced expression of the mannose receptor (CD206, allows detection of bacteria), increase phagocytosis of inert beads/macrophages. Moreover, CGRP increases VEGF and CCL18 expression in M(IL4), and soluble mediators from these cells promoted in vitro epithelial wound repair. Conclusions Reduced expression of CGRP and its receptor has been shown in IBD. The findings herein, demonstrating how CGRP-RAMP1 signalling can reinforce and enhance a regulatory, reparatory phenotype in human macrophages reveals another aspect of IBD pathophysiology. We speculate that loss of this neuroimmune axis (i.e. CGRP/Nerve-M(IL4) interaction) has the potential to significantly impair mucosal healing in IBD. Funding Agencies CCCAlberta Innovates in Health Innovation

APA, Harvard, Vancouver, ISO, and other styles

14

Morris, Gerwyn, Ken Walder, Basant K. Puri, Michael Berk, and Michael Maes. "The Deleterious Effects of Oxidative and Nitrosative Stress on Palmitoylation, Membrane Lipid Rafts and Lipid-Based Cellular Signalling: New Drug Targets in Neuroimmune Disorders." Molecular Neurobiology 53, no. 7 (August 27, 2015): 4638–58. http://dx.doi.org/10.1007/s12035-015-9392-y.

Full text

APA, Harvard, Vancouver, ISO, and other styles

15

Pereira, Sónia R., Becky Hackett, David N. O’Driscoll, Melody Cui Sun, and Eric J. Downer. "Cannabidiol modulation of oxidative stress and signalling." Neuronal Signaling 5, no. 3 (August 24, 2021). http://dx.doi.org/10.1042/ns20200080.

Full text

Abstract:

Abstract Cannabidiol (CBD), one of the primary non-euphoric components in the Cannabis sativa L. plant, has undergone clinical development over the last number of years as a therapeutic for patients with Lennox-Gastaut syndrome and Dravet syndromes. This phytocannabinoid demonstrates functional and pharmacological diversity, and research data indicate that CBD is a comparable antioxidant to common antioxidants. This review gathers the latest knowledge regarding the impact of CBD on oxidative signalling, with focus on the proclivity of CBD to regulate antioxidants and control the production of reactive oxygen species. CBD is considered an attractive therapeutic agent for neuroimmune disorders, and a body of literature indicates that CBD can regulate redox function at multiple levels, with a range of downstream effects on cells and tissues. However, pro-oxidant capacity of CBD has also been reported, and hence caution must be applied when considering CBD from a therapeutic standpoint. Such pro- and antioxidant functions of CBD may be cell- and model-dependent and may also be influenced by CBD dose, the duration of CBD treatment and the underlying pathology.

APA, Harvard, Vancouver, ISO, and other styles

16

Nelvagal, Hemanth R., Maica Llavero Hurtado, Samantha L. Eaton, Rachel A. Kline, Douglas J. Lamont, Mark S. Sands, Thomas M. Wishart, and Jonathan D. Cooper. "Comparative proteomic profiling reveals mechanisms for early spinal cord vulnerability in CLN1 disease." Scientific Reports 10, no. 1 (September 16, 2020). http://dx.doi.org/10.1038/s41598-020-72075-7.

Full text

Abstract:

Abstract CLN1 disease is a fatal inherited neurodegenerative lysosomal storage disease of early childhood, caused by mutations in the CLN1 gene, which encodes the enzyme Palmitoyl protein thioesterase-1 (PPT-1). We recently found significant spinal pathology in Ppt1-deficient (Ppt1−/−) mice and human CLN1 disease that contributes to clinical outcome and precedes the onset of brain pathology. Here, we quantified this spinal pathology at 3 and 7 months of age revealing significant and progressive glial activation and vulnerability of spinal interneurons. Tandem mass tagged proteomic analysis of the spinal cord of Ppt1−/−and control mice at these timepoints revealed a significant neuroimmune response and changes in mitochondrial function, cell-signalling pathways and developmental processes. Comparing proteomic changes in the spinal cord and cortex at 3 months revealed many similarly affected processes, except the inflammatory response. These proteomic and pathological data from this largely unexplored region of the CNS may help explain the limited success of previous brain-directed therapies. These data also fundamentally change our understanding of the progressive, site-specific nature of CLN1 disease pathogenesis, and highlight the importance of the neuroimmune response. This should greatly impact our approach to the timing and targeting of future therapeutic trials for this and similar disorders.

APA, Harvard, Vancouver, ISO, and other styles

17

Pradhan, Leena, Christoph Nabzdyk, Nicholas D. Andersen, Frank W. LoGerfo, and Aristidis Veves. "Inflammation and neuropeptides: the connection in diabetic wound healing." Expert Reviews in Molecular Medicine 11 (January 2009). http://dx.doi.org/10.1017/s1462399409000945.

Full text

Abstract:

Abnormal wound healing is a major complication of both type 1 and type 2 diabetes, with nonhealing foot ulcerations leading in the worst cases to lower-limb amputation. Wound healing requires the integration of complex cellular and molecular events in successive phases of inflammation, cell proliferation, cell migration, angiogenesis and re-epithelialisation. A link between wound healing and the nervous system is clinically apparent as peripheral neuropathy is reported in 30–50% of diabetic patients and is the most common and sensitive predictor of foot ulceration. Indeed, a bidirectional connection between the nervous and the immune systems and its role in wound repair has emerged as one of the focal features of the wound-healing dogma. This review provides a broad overview of the mediators of this connection, which include neuropeptides and cytokines released from nerve fibres, immune cells and cutaneous cells. In-depth understanding of the signalling pathways in the neuroimmune axis in diabetic wound healing is vital to the development of successful wound-healing therapies.

APA, Harvard, Vancouver, ISO, and other styles

18

Dedek, Annemarie, Jian Xu, Louis-Étienne Lorenzo, Antoine G. Godin, Chaya M. Kandegedara, Geneviève Glavina, Jeffrey A. Landrigan, et al. "Sexual dimorphism in a neuronal mechanism of spinal hyperexcitability across rodent and human models of pathological pain." Brain, March 23, 2022. http://dx.doi.org/10.1093/brain/awab408.

Full text

Abstract:

Abstract The prevalence and severity of many chronic pain syndromes differ across sex, and recent studies have identified differences in immune signalling within spinal nociceptive circuits as a potential mediator. Although it has been proposed that sex-specific pain mechanisms converge once they reach neurons within the superficial dorsal horn, direct investigations using rodent and human preclinical pain models have been lacking. Here, we discovered that in the Freund’s adjuvant in vivo model of inflammatory pain, where both male and female rats display tactile allodynia, a pathological coupling between KCC2-dependent disinhibition and N-methyl-D-aspartate receptor (NMDAR) potentiation within superficial dorsal horn neurons was observed in male but not female rats. Unlike males, the neuroimmune mediator brain-derived neurotrophic factor (BDNF) failed to downregulate inhibitory signalling elements (KCC2 and STEP61) and upregulate excitatory elements (pFyn, GluN2B and pGluN2B) in female rats, resulting in no effect of ex vivo brain-derived neurotrophic factor on synaptic NMDAR responses in female lamina I neurons. Importantly, this sex difference in spinal pain processing was conserved from rodents to humans. As in rodents, ex vivo spinal treatment with BDNF downregulated markers of disinhibition and upregulated markers of facilitated excitation in superficial dorsal horn neurons from male but not female human organ donors. Ovariectomy in female rats recapitulated the male pathological pain neuronal phenotype, with BDNF driving a coupling between disinhibition and NMDAR potentiation in adult lamina I neurons following the prepubescent elimination of sex hormones in females. This discovery of sexual dimorphism in a central neuronal mechanism of chronic pain across species provides a foundational step towards a better understanding and treatment for pain in both sexes.

APA, Harvard, Vancouver, ISO, and other styles

19

Guennewig, Boris, Julia Lim, Lee Marshall, Andrew N. McCorkindale, Patrick J. Paasila, Ellis Patrick, Jillian J. Kril, Glenda M. Halliday, Antony A. Cooper, and Greg T. Sutherland. "Defining early changes in Alzheimer’s disease from RNA sequencing of brain regions differentially affected by pathology." Scientific Reports 11, no. 1 (March 1, 2021). http://dx.doi.org/10.1038/s41598-021-83872-z.

Full text

Abstract:

AbstractTau pathology in Alzheimer’s disease (AD) spreads in a predictable pattern that corresponds with disease symptoms and severity. At post-mortem there are cortical regions that range from mildly to severely affected by tau pathology and neuronal loss. A comparison of the molecular signatures of these differentially affected areas within cases and between cases and controls may allow the temporal modelling of disease progression. Here we used RNA sequencing to explore differential gene expression in the mildly affected primary visual cortex and moderately affected precuneus of ten age-, gender- and RNA quality-matched post-mortem brains from AD patients and healthy controls. The two regions in AD cases had similar transcriptomic signatures but there were broader abnormalities in the precuneus consistent with the greater tau load. Both regions were characterised by upregulation of immune-related genes such as those encoding triggering receptor expressed on myeloid cells 2 and membrane spanning 4-domains A6A and milder changes in insulin/IGF1 signalling. The precuneus in AD was also characterised by changes in vesicle secretion and downregulation of the interneuronal subtype marker, somatostatin. The ‘early’ AD transcriptome is characterised by perturbations in synaptic vesicle secretion on a background of neuroimmune dysfunction. In particular, the synaptic deficits that characterise AD may begin with the somatostatin division of inhibitory neurotransmission.

APA, Harvard, Vancouver, ISO, and other styles

20

Chaudhry, I. B., M. O. Husain, A. B. Khoso, M. I. Husain, M. H. Buch, T. Kiran, B. Fu, et al. "A randomised clinical trial of methotrexate points to possible efficacy and adaptive immune dysfunction in psychosis." Translational Psychiatry 10, no. 1 (November 30, 2020). http://dx.doi.org/10.1038/s41398-020-01095-8.

Full text

Abstract:

AbstractNMDA autoantibody encephalitis presenting as schizophrenia suggests the possible role of adaptive cell-mediated immunity in idiopathic schizophrenia. However, to our knowledge there have been no trials of the immune-suppressant methotrexate in schizophrenia. We tested if low-dose methotrexate as used in the treatment of systemic autoimmune disorders would be tolerable and effective in people with schizophrenia in a feasibility study. Ninety-two participants within 5 years of schizophrenia diagnosis were recruited from inpatient and outpatient facilities in Karachi, Pakistan. They were randomised to receive once weekly 10-mg oral methotrexate (n = 45) or matching placebo (n = 47) both with daily 5-mg folic acid, in addition to treatment as usual for 12 weeks. There were eight dropouts per group. Side effects were non-significantly more common in those on methotrexate and were not severe. One person developed leukopenia. Positive symptom scores improved more in those receiving methotrexate than placebo (β = −2.5; [95% CI −4.7 to −0.4]), whereas negative symptoms were unaffected by treatment (β = −0.39; [95% CI −2.01 to 1.23]). There were no immune biomarkers but methotrexate did not affect group mean leucocyte counts or C-reactive protein. We conclude that further studies are feasible but should be focussed on subgroups identified by advances in neuroimmune profiling. Methotrexate is thought to work in autoimmune disorders by resetting systemic regulatory T-cell control of immune signalling; we show that a similar action in the CNS would account for otherwise puzzling features of the immuno-pathogenesis of schizophrenia.

APA, Harvard, Vancouver, ISO, and other styles

Journal articles on the topic 'Neuroimmune signalling'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles