Дисертації з теми "Neurogenetic syndrome"
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся з топ-20 дисертацій для дослідження на тему "Neurogenetic syndrome".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Переглядайте дисертації для різних дисциплін та оформлюйте правильно вашу бібліографію.
Pierre, Constance. "Conséquences fonctionnelles, comportementales et adaptatives d'une mutation de la MAO (MonoAmine Oxydase) chez le poisson cavernicole aveugle Astyanax mexicanus. A Mutation in Monoamine Oxidase (MAO) Affects the Evolution of Stress Behavior in the Blind Cavefish Astyanax Mexicanus." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASS084.
Повний текст джерелаThe neurotransmitter serotonin controls a great variety of physiological and behavioral processes. In humans, mutations affecting the monoamine oxidase or MAO, the serotonin-degrading enzyme, are highly deleterious. Yet, blind cavefish of the species A. mexicanus carry a partial loss-of-function mutation in MAO (P106L) and seem to thrive in their subterranean environ-ment. This thesis describes the effects of this mutation, from the molecular level to the population level, in order to decipher the exact contribution of mao P106L in the evolution of cavefish neuro-behavioral traits, during their adaptation to the cave environment.In a first paper, we established 4 fish lines, corresponding to the blind cave-dwelling and the sighted river-dwelling morphs of this species, with or without the mutation. We found that mao P106L strongly affected anxiety-like behaviors. Cortisol measurements showed lower basal levels and an increased amplitude of stress response after a change of environment in fish carrying the mutation. Finally, we studied the distribution of the P106L mao allele in wild populations of cave and river A. mexicanus, and discovered that the mutant allele was present – and sometimes fixed - in all populations inhabiting caves of the Sierra de El Abra. The possibility that this partial loss-of-function mao allele evolves under a selective or a genetic drift regime in the particular cave environment is discussed.In a second paper, we assessed the structural and biochemical consequences of the mutation. We found that the reduction of enzymatic activity of mutant MAO is probably caused by a decrease of flexibility in one of the three loops forming the entrance of the active site, thus reducing the access of substrates. HPLC measurements in brains of mutant and non-mutant larvae and adult fish showed major disturbances in serotonin, dopamine and noradrenalin (and metabolites) contents, demonstrating that the P106L mao mutation is fully responsible for monoaminergic disequilibrium in the cavefish brain. We also discovered that the effects of the mutation were partially compensated by a decrease in activity of the TPH, the serotonin biosynthesis rate-limiting enzyme. Our results shade light on the specificities of fish monoaminergic systems.Finally in order to aggravate the MAO inhibition, we generated the first fish knockout MAO mutant. The KO homozygous mutants were stunted and died during the first weeks of development. Contrary to the dopaminergic system which seemed normal in the KO homozygous mutants, the serotonergic system was strongly impaired; no serotonin positive neuron was detected in the hypothalamus
Fila, Tatiana <1978>. "Neurogenesis impairment and cell cycle alterations in Down Syndrome." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2008. http://amsdottorato.unibo.it/990/.
Повний текст джерелаPons, Espinal Meritxell 1986. "Role of DYRK1A in hippocampal neuroplasticity : implications for Down syndrome." Doctoral thesis, Universitat Pompeu Fabra, 2013. http://hdl.handle.net/10803/124485.
Повний текст джерелаLes connexions sinàptiques tenen la capacitat de respondre a l’activitat de neurones ajustant les seves propietats biològiques per incrementar els canvis activitat-depenents. Alteracions en la plasticitat neuronal de l’hipocamp s'han suggerit com a mecanismes subjacents als deterioraments cognitius característics en la síndrome de Down (SD). No obstant, es desconeix quins gens específics estan implicats en aquests fenotips en el context de la trisomia del cromosoma 21. DYRK1A és una serina / treonina quinasa, que quan es troba sobreexpressada recapitula el dèficit d'aprenentatge i de memòria depenent de l'hipocamp característic de la SD. En aquesta tesi, s’han estudiat els efectes de la sobreexpressió de DYRK1A en la plasticitat activitat-dependent de l’hipocamp. Hem descobert que ratolins transgènics amb sobreexpressió de Dyrk1A (TgDyrk1A) presenten alteracions morfològiques en les regions CA1 i CA3 de l'hipocamp, una limitació estructural en les connexions neuronals que és rellevant per entendre la relació entre estructura i funció. A més, hem trobat una reducció en la LTP possiblement deguda als canvis en la connectivitat i ocupació dendrítica. L’excitabilitat de les dendrites i la morfologia neuronal són factors determinants de l'eficàcia sinàptica i per tant poden contribuir als dèficits d'aprenentatge i la memòria de l'hipocamp detectats. Hem demostrat defectes importants en la neurogènesi adulta en el gir dentat incloent una reduïda taxa de proliferació cel·lular, alteracions en el cicle cel·lular i reducció de cèl·lules que surten del cicle cel·lular que condueix a una migració precoç de les noves cèl·lules generades i una reducció de la supervivència. D'altra banda, en ratolins TgDyrk1A hi ha menys proporció de neurones generades de novo que s'activen amb l'aprenentatge, indicant una menor integració d’aquestes en els circuits implicats en l'aprenentatge. Algunes d'aquestes alteracions han estat rescatades per la normalització de DYRK1A quinasa utilitzant un inhibidor de DYRK1A, epigallocatechin-3-gallate. L'estimulació del medi ambient també normalitza la sobreexpressió de DYRK1A quinasa en l'hipocamp, i rescata la morfologia, la plasticitat sinàptica i les alteracions en la neurogènesi adulta en ratolins TgDyrk1A. Arribem a la conclusió que Dyrk1A és un bon gen candidat per explicar els dèficits de plasticitat neuronal en la SD i que tractant l’excés d'activitat de la quinasa DYRK1A farmacològicament o mitjançant l'estimulació ambiental en l'adult podria corregir aquests defectes en la SD.
Bianchi, Patrizia <1979>. "Defective neurogenesis in the Ts65Dn mouse, a model for Down syndrome, can be restored by pharmacological treatments." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2010. http://amsdottorato.unibo.it/3139/.
Повний текст джерелаModyanova, Nadezhda N. "Semantic and pragmatic language development in typical acquisition, autism spectrum disorders, and Williams syndrome with reference to developmental neurogenetics of the latter." Thesis, Massachusetts Institute of Technology, 2009. http://hdl.handle.net/1721.1/57547.
Повний текст джерелаThis electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student submitted PDF version of thesis.
Includes bibliographical references.
The elucidation of the biological bases of a complex trait like human language proceeds from identification of precise behavioral phenotypes to investigation of the underlying genes. The human behavioral parts of this dissertation focus on understanding the reasons for children's overuse of definite article 'the', to refer to one of several objects in a context set, as opposed to the unique established referent. Competing theories argue the deficit is either in children's semantic computational knowledge (of uniqueness/maximality), or in their pragmatic/social awareness/theory-of-mind development. Experiments in this dissertation focused on children's comprehension and interpretation of the indefinite and definite determiners, as well as 'that', anaphors 'another' and 'same', and free relative clauses. The results in this thesis suggest that in typically developing (TD) children the late acquisition of determiner 'the' is due to the late maturation of the semantic principle of maximality. Children with autism spectrum disorders (ASD) and with Williams syndrome (WS) either manifested an adult-like competence, an absence of manifestation of knowledge, or a pattern found in TD younger children (where 'that' is understood better than 'the' as referring to the salient unique referent) -- indicating delay of development of the language faculty, but no deviance. This suggests that the observed deficits in ASD and WS pattern with those in TD, and hence are also semantic in nature. The mouse neurogenetic part of this dissertation investigates whether the GTF2I family of genes, causal to WS behavioral phenotype, also contributes to WS cortical development.
(cont.) By overexpression of Gtf2i and Gtf2ird1 in the mouse neocortex via in utero electroporation, their effects on laminar patterning and cell morphogenesis during brain development are characterized. The present results suggest that these genes can synergistically contribute to the abnormal neocortical development in WS, and thereby could contribute to language deficits in WS. Beyond posing an explanatory challenge to linguistic theories, the research comparing typical and atypical development sheds light on the mechanisms of language development and impairment, and provides endophenotypic descriptions of ASD and WS, which are crucial for elucidating not only genetics of neurodevelopmental disorders, but also the genetic basis of the human language faculty.
by Nadezhda N. Modyanova.
Ph.D.
Vithayathil, Joseph. "Developmental and Post-natal Roles for ERK1/2 Signaling in the Hippocampus." Case Western Reserve University School of Graduate Studies / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1435760090.
Повний текст джерелаLunion, Steeve. "Enrichissement environnemental, performances cognitives et neurogenèse hippocampique adulte chez un modèle murin du syndrome de Coffin-Lowry." Thesis, Paris 11, 2014. http://www.theses.fr/2014PA11T034/document.
Повний текст джерелаThe Coffin-Lowry Syndrome is a rare syndromic form of X-linked intellectual disability. This syndrome is caused by mutations of the Rsk2 gene that encodes a protein kinase, RSK2, in the MAPK/ERK signaling pathway. Characterization of the behavioural phenotype of Rsk2-KO mice mainly showed that they display delayed acquisition and long-term deficits in a spatial reference memory task, suggesting an alteration in hippocampal function. Here, we show that Rsk2-KO mice are also deficient in a learning and memory task that involves dentate gyrus-dependent pattern separation function. Several studies showed the formation of new neurons in the adult dentate gyrus by neurogenesis is a form of plasticity that plays a significant role in hippocampal-dependent learning and memory, in particular for spatial learning and memory and pattern separation. As these functions are altered in Rsk2-KO mice, we studied hippocampal adult neurogenesis in these mice. No difference in proliferation, survival and maturation of newborn neurons was found in the dentate gyrus of the mutant mice in basal conditions, nor after a pattern separation task. However, we found a deficit in the survival of newborn cells in Rsk2-KO mice submitted to spatial learning and memory in the Morris water maze task. According to several studies, environmental enrichment in rodents has beneficial effects on cognitive performance and is associated with an enhancement of adult hippocampal neurogenesis. Thus, we assessed the potential effect of environmental enrichment on spatial learning and memory performance and adult hippocampal neurogenesis in Rsk2-KO mice. Our results show that an environmental enrichment protocol of 3h per day during 24 days can rescue or ameliorate spatial learning and memory performance and pattern separation function in Rsk2-KO mice and increase adult hippocampal neurogenesis
Najas, Sales Sònia 1985. "Role of DYRK1A in the development of the cerebral cortex : Implication in Down Syndrome." Doctoral thesis, Universitat Pompeu Fabra, 2014. http://hdl.handle.net/10803/380895.
Повний текст джерелаEn aquest treball s'ha avaluat la possible contribució del gen DYRK1A, localitzat en el cromosoma humà 21, en les alteracions del desenvolupament de l’escorça cerebral associades a la Síndrome de down (SD) mitjançant l’estudi de dos models murins: el ratolí mBACTgDyrk1a, el qual conté 3 còpies de Dyrk1a, i el ratolí Ts65Dn, un dels models trisòmics de la SD més ben caracteritzats. Els nostres resultats mostren que la trisomia de Dyrk1A altera alguns paràmetres del cicle cel•lular i el tipus de divisió dels progenitors neurals del telencèfal dorsal, donant lloc a un dèficit de neurones glutamatèrgiques que persisteix fins l’edat adulta. Hem demostrat que Dyrk1a és el gen triplicat responsable del dèficit inicial en la generació de neurones glutamatèrgiques corticals observat en el ratolí Ts65Dn. A més a més, hem proporcionat evidències de que la degradació de Ciclina D1 induïda per DYRK1A és el mecanisme molecular subjacent a les alteracions de cicle cel•lular observades en els progenitors neuronals dels embrions mBACTgDyrk1a i Ts65Dn. Per altra banda, hem demostrat que la neurogènesis inicial està incrementada en l’eminència ganglionar medial dels embrions mBACTgDyrk1a, fet que altera la proporció de subtipus específics d’interneurones GABAèrgiques en l’escorça cerebral adulta. En conclusió, els nostres resultats indiquen que la sobreexpressió de DYRK1A contribueix significativament a la formació dels circuits cortical en la SD.
Bernardet, Maude. "Etude des traits autistiques chez un modèle souris du X Fragile." Thesis, Bordeaux 1, 2008. http://www.theses.fr/2008BOR13749/document.
Повний текст джерелаAutism is a pervasive developmental disorder defined by behavioural criteria and age of onset. Fragile X is a disorder due to the silencing of the Fmr1 gene. About 15-25% of Fragile X patients are diagnosed as autistic and many symptoms overlap between the two disorders. A mouse Fmr1 KO was created and validated as a model for Fragile X Syndrome. Preliminary data also show that the null mutation interacts with the genetic background. The work presented in this thesis aimed to determine the autistic features expressed in Fmr1 KO mice, as well as the influence of the genetic background (C57BL/6J and FVB.129P2tm1Cgr/J strains, and their reciprocal hybrids) on the expression of the Fmr1 mutation. Our results show an initial inhibition of social approach in Fmr1 KO mice and a qualitative alteration of ultrasonic vocalizations in isolated pups, as well as an increase in activity, especially during the diurnal period. The Fmr1 mutation interacts with the genetic background and the results indicate that KO on the FVB.129P2tm1Cgr/J background show the most marked phenotype
Cavallin, Mara. "Physiopathologie moléculaire et cellulaire des anomalies du développement du cortex cérébral : le syndrome d'Aicardi WDR81 mutations cause extreme microcephaly and impair mitotic progression in human fibroblasts and Drosophila neural stem cells TLE1, a key player in neurogenesis, a new candidate gene for autosomal recessive postnatal microcephaly Mutations in TBR1 gene leads to cortical malformations and intellectual disability Aicardi syndrome: Exome, genome and RNA-sequencing of a large cohort of 19 patients failed to detect the genetic cause Recurrent RTTN mutation leading to severe microcephaly, polymicrogyria and growth restriction Recurrent KIF2A mutations are responsible for classic lissencephaly Recurrent KIF5C mutation leading to frontal pachygyria without microcephaly Rare ACTG1 variants in fetal microlissencephaly De novo TUBB2B mutation causes fetal akinesia deformation sequence with microlissencephaly: An unusual presentation of tubulinopathy A novel recurrent LIS1 splice site mutation in classic lissencephaly Further refinement of COL4A1 and COL4A2 related cortical malformations Prenatal and postnatal presentations of corpus callosum agenesis with polymicrogyria caused By EGP5 mutation Delineating FOXG1 syndrome from congenital microcephaly to hyperkinetic encephalopathy Delineating FOXG1 syndrome: From congenital microcephaly to hyperkinetic encephalopathy." Thesis, Sorbonne Paris Cité, 2019. https://wo.app.u-paris.fr/cgi-bin/WebObjects/TheseWeb.woa/wa/show?t=2213&f=18201.
Повний текст джерелаMalformations of cortical development (MCD) are a major cause of intellectual disability and drug-resistant epilepsy. Next Generation Sequencing (NGS) has considerably improved the identification of the molecular basis of non-syndromic MCD. However, certain forms, including complex MCD, remain unexplained. My PhD project aimed to improve the understanding of complex MCD using two disorders: Microlissencephaly (MLIS) and Aicardi Syndrome (AIC), the latter associating brain and eye malformations and only reported in girls. Trio Whole Exome Sequencing (WES) performed in 16 MLIS families allowed me to identify and functionally characterize a new MLIS gene, WDR81, in which mutations lead to cell cycle alteration. Moreover, using the same strategy, I was able to identify a pathogenic homozygous variant in TLE1 in a patient from consanguineous family with a postnatal microcephaly, suggestive of a FOXG1-like presentation. Interestingly, TLE1 is a major partner of FOXG1, a gene involved in maintaining the balance between progenitor proliferation and differentiation. In parallel, my work allowed me to redefine the phenotypic spectrum associated with RTTN, EPG5, COL4A1 and COL4A2, TBR1, KIF5C, KIF2A and FOXG1. The second part of my PhD program was aimed at identifying the genetic basis of AIC in an international cohort of 19 patients. After excluding a skewed X chromosome inactivation and the presence of chromosomal rearrangements, I performed WES in trios. The analysis of the data from WES did not allow me to identify any recurrent variants. I therefore tested a new approach combining Whole Genome Sequencing (WGS) and RNA-Sequencing (RNA-Seq) on fibroblast cells. I identified a number of deregulated transcripts implicated in brain and eye development. I compared the results of this analysis with the WGS analysis in order to find variants in these candidate genes. In conclusion, these studies have improved the knowledge of the molecular basis of complex MCD, such as TLE1 in postnatal microcephaly, and revealed the pathogenic mechanisms such as WDR81 in cell cycle progression and EPG5 in endosomes and autophagy. My work has also generated a collection of NGS data (WES, WGS and RNA-Seq) that will be shared in an international consortium to develop new analytical strategies, in particular for the non-coding DNA regions. This novel strategy provides opportunities to improve understanding of the cellular mechanisms involved in brain and eye development
Silva, Ana Paula de Abreu e. "Mutações inativadoras dos genes PROK2 e PROKR2 em pacientes com hipogonadismo hipogonadotrófico isolado." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5135/tde-18022011-134611/.
Повний текст джерелаPhysiological activation of the prokineticin pathway has a critical role in olfactory bulb morphogenesis and GnRH secretion. Knock-out mice for genes that encode prokineticin 2 (PROK2) and the prokineticin receptor 2 (PROKR2) exhibited a phenotype similar to the Kallmann syndrome (KS). Inactivating mutations in PROK2 and PROKR2 have been identified in patients with isolated hypogonadotropic hypogonadism. Based on these findings, we investigated the presence of inactivating mutations of the genes PROK2 and PROKR2 in Brazilian patients with isolated hypogonadotropic hypogonadism associated or not with olfactory abnormalities and performed in vitro studies of the new identified mutations. We studied 107 patients with HH (63 with Kallmann syndrome and 44 with normosmic HH) and 100 control individuals. The coding regions of PROK2 and PROKR2 were amplified by polymerase chain reaction followed by enzymatic purification and direct automatic sequencing. In PROK2, two known frameshift mutations were identified. Two brothers with Kallmann syndrome harbored the homozygous p.G100fsX121 mutation, whereas one male with normosmic HH harbored the heterozygous p.I55fsX56 mutation. In PROKR2, four distinct mutations (p.R80C, p.Y140X, p.L173R and p.R268C) were identified in five patients with Kallmann syndrome and in one patient with normosmic HH. These mutations were not found in the control group. The p.R80C and p.R268C missense mutations were identified in heterozygous state in the HH patients and in their asymptomatic first-degree relatives. The p.L173R was also identified in heterozygous state. In addition, no mutations of FGFR1, GnRHR, KiSS-1 or GPR54 were identified in these patients. The patient with the PROKR2 mutation p.R268C also has a deletion of the exon 1 and 2 in the gene KAL1. Notably, the new nonsense mutation (p.Y140X) was identified in homozygous state in an anosmic boy with micropenis, bilateral cryptorchidism and high-arched palate. His asymptomatic parents were heterozygous for this severe defect. In vitro studies of the new mutation, p.R80C, were performed in order to access the mechanism by which this mutation could affect the activity of the PROKR2. In vitro studies showed that the amount of fofatidil-inositol (PI) and the activation of MAPK were significantly lower in cells transfected with the R80C mutant receptor than in cells transfected with the wild receptor, indicating that this variant is a loss-of-function mutation. Binding studies and Western blot showed a reduction in the expression levels of the receptor in the plasma membrane and in whole cell, respectively. Additionally, Western blot analysis of R80C PROKR2 revealed an additional smaller molecular weight band that represents the presence of immature unglycosylated receptors. The arginine 80 in ICL1 is important for post-translational processing of PROKR2. In conclusion, we expanded the repertoire of PROK2 and PROKR2 mutations in patients with HH and showed that PROKR2 haploinsufficiency is not sufficient to cause Kallmann syndrome or normosmic HH, whereas homozygous loss-of-function mutations either in PROK2 or PROKR2 are sufficient to cause disease phenotype, in accordance with the Prokr2 and Prok2 knockout mouse models. In vitro studies suggested that the arginine located at position 80 of the receptor seems to play an important role in the receptor function
Girard, Simon L. "Étude sur le rôle des déséquilibres génomiques dans le Syndrome d’Impatiences Musculaires de l’Éveil." Thèse, 2010. http://hdl.handle.net/1866/4115.
Повний текст джерелаRestless Legs syndrome (RLS) is a neurological disorder characterized by the urge to move one’s limbs. It is also one of the most frequent causes of insomnia. The prevalence of RLS is estimated to be around 15% in the general population. Complexes disorders like RLS are often the result of the evolution of genetic and environmental components. For RLS, recent Genome Wide Association Study (GWAS) have identified four variants with mild to moderate effects. However, those four variants explain only a small part of the disease heritability and thus, we expect that many new variants are still to be found. The impact of Copy-Number Variation (CNV) in the genetic mechanism of RLS is still unknown. However, many studies have recently position the CNVs as a significant source of genetic variation potentially responsible of phenotypes. In collaboration with a team from Munich, we conducted two genome-wide CNVs studies (Genome Wide SNP chips and Comparative Genomic Hybridization (CGH)) on RLS patients from Germany. Using cases-controls studies, we identified regions with a different occurrence of CNVs for RLS patients, compared to different groups of controls. One of these regions is particularly interesting, as it has already been identified by both linkage and association studies.
Hsu, Jui-Hong, and 徐瑞鴻. "Study on the effects of Scn1a mutation (Dravet syndrome) in neurogenesis." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/71846580913041455264.
Повний текст джерела國立臺灣大學
藥理學研究所
103
Dravet syndrome is a refractory seizure characterized by severe infant-onset myoclonic epilepsy, delayed psychomotor development and autism-spectrum behaviours. Loss-of-function mutations in Scn1a gene which encodes the type Ⅰvoltage-gated sodium channel (Nav1.1) is the predominant molecular cause in most patients. Children with Dravet syndrome are significantly impaired in visuo-perceptual skill performance, and the spatial memory have been reported close relative to hippocampus neurogenesis. However, the underlying dysfunction of the Scn1a gene might confer to the brain neurogenesis is largely unknown. Here, we constructed a transgenic mice with Scn1a1099X knock-in (KI) allele which presented an animal model of Dravet syndrome, exhibited spontaneous epileptic discharges and susceptible to hyperthermia-induced seizures. Our results show that Nav1.1 deficiency lead to significant increase in neural stem cell-derived neurospheres number and accompanied with increasing neural stem cell (NSC) marker, GFAP. Quantification of cell division with the proliferation indicator, Ki67 or PCNA, showed that cell proliferation was significant increase result from Nav1.1 dysfunction. Measurement of [Ca2+]i by fura-2 AM Ca2+ imaging demonstrated that [Ca2+]i was markedly elevated in neurospheres derived from Scn1a mutation mice. NSC are characterized as cells with potential to produce a large amount of progeny that grow and differentiate into neuron, astrocyte and oligodendrocyte. Immunocytochemistry result indicated that loss of Nav1.1 in NSC result in significant increase the neuroblast and immature neuron but oligodendrocyte in neurosphere-derived cells which isolated from postnatal day 1 mice. In contrast, NSC obtained from postnatal day 8 Scn1a-deficit animal showed an upregulation of immature neuron and oligodendrocyte lineage but neuroblast. Moreover, prolonged differentiation for 2 weeks of neurosphere-derived cell culture isolated from postnatal day 1 Scn1a-mutant mice revealed that the ratio of mature neuron and GABAergic neuron were dramatically increased. GABA has been known to regulate neurogenesis, thus we further to investigate the effects of GABA on Scn1a deficiency neurosphere. Our results show that GABA promote neurosphere formation in PD1 neurosphere, but inhibit neurosphere formation in PD8 neurosphere. When neurosphere were induced to differentiation for 5 days, we found abnormal neuronal differentiation were reverse by GABA. These results revealed that loss of Scn1a gene might contribute to promote NSCs differentiate into neuronal series. Our results support that Scn1a gene play an important role in postnatal neuronal development.
Brady, Morgan. "Abnormal neurogenesis and gliogenesis in the developing spinal cord in a mouse model of Down syndrome." Thesis, 2018. https://hdl.handle.net/2144/30912.
Повний текст джерелаRydzyková, Tereza. "Vliv morfinu na neurogenezi a neurodegeneraci v mozku potkana." Master's thesis, 2017. http://www.nusl.cz/ntk/nusl-367807.
Повний текст джерелаBoehme, Fanny. "The effects of voluntary exercise on adult hippocampal neurogenesis and BDNF levels in a rodent model of fetal alcohol spectrum disorders." Thesis, 2010. http://hdl.handle.net/1828/3327.
Повний текст джерелаGraduate
Kaufman, Liana. "Identification of Non-syndromic Intellectual Disability Genes and Their Overlap with Autism." Thesis, 2011. http://hdl.handle.net/1807/29568.
Повний текст джерелаAziz, Nadine M. "Histological, cellular, and molecular abnormalities in forebrain and spinal cord of three distinct mouse models of Down syndrome." Thesis, 2017. https://hdl.handle.net/2144/23413.
Повний текст джерела2018-07-09T00:00:00Z
Stringer, Megan Elizabeth. "Effect of Epigallocatechin-3-gallate on a pattern separation task and hippocampal neurogenesis in a mouse model of Down syndrome." Thesis, 2015. http://hdl.handle.net/1805/10037.
Повний текст джерелаDown syndrome (DS) is caused by three copies of human chromosome 21 (Hsa21) and results in an array of phenotypes including intellectual disability. Ts65Dn mice, the most extensively studied DS model, have three copies of ~50% of the genes on Hsa21 and display many phenotypes associated with DS, including cognitive deficits. DYRK1A is found in three copies in humans with Trisomy 21 and in Ts65Dn mice, and is involved in a number of critical pathways including CNS development and osteoclastogenesis. Epigallocatechin-3-gallate (EGCG), the main polyphenol in green tea, inhibits Dyrk1a activity. We have shown that a three-week EGCG treatment (~10mg/kg/day) during adolescence normalizes skeletal abnormalities in Ts65Dn mice, yet the same dose did not rescue deficits in the Morris water maze spatial learning task (MWM) or novel object recognition (NOR). Others have reported that An EGCG dose of 2-3 mg per day (90mg/ml) improved hippocampal-dependent task deficits in Ts65Dn mice. The current study investigated deficits in a radial arm maze pattern separation task in Ts65Dn mice. Pattern separation requires differentiation between similar memories acquired during learning episodes; distinguishing between these similar memories is thought to depend on distinctive encoding in the hippocampus. Pattern separation has been linked to functional activity of newly generated granule cells in the dentate gyrus. Recent studies in Ts65Dn mice have reported significant reductions in adult hippocampal neurogenesis, and after EGCG treatment, enhanced hippocampal neurogenesis. Thus, it was hypothesized that Ts65Dn mice would be impaired in the pattern separation task, and that EGCG would alleviate the pattern separation deficits seen in trisomic mice, in association with increased adult hippocampal neurogenesis. At weaning, Ts65Dn mice and euploid littermates were randomly assigned to the water control, or EGCG [0.4 mg/mL], with both treatments yielding average daily intakes of ~50 mg/kg/day. Beginning on postnatal day 75, all mice were trained on a radial arm maze-delayed non-matching-to-place pattern separation task. Euploid mice performed significantly better over training than Ts65Dn mice, including better performance at each of the three separations. EGCG did not significantly alleviate the pattern separation deficits in Ts65Dn mice. After the behavioral testing commenced, animals were given ad libitum food access for five days, received a 100mg/kg injection of BrdU, and were perfused two hours later. Coronal sections through the dorsal hippocampus were processed for BrdU labeling, and cells were manually counted throughout the subgranular zone of the dentate gyrus. The euploid controls had significantly more BrdU labeled cells than Ts65Dn mice, however, EGCG does not appear to increase proliferation of the hippocampal neuroprogenitor cells. This is the first report of deficits in Ts65Dn mice on a pattern separation task. To the extent that pattern separation depends on the functional involvement of newly generated neurons in an adult dentate gyrus, this approach in Ts65Dn mice may help identify more targeted pharmacotherapies for cognitive deficits in individuals with DS.
Abdulnour, Shahad. "Effect of Dopamine Receptor DRD2 and ANKK1 Polymorphisms on Dietary Compliance, Blood Pressure, and BMI in Type 2 Diabetic Patients." Thesis, 2010. http://hdl.handle.net/1807/25396.
Повний текст джерела