Similar Datasets
Project description:NMDA (N-methyl-d-aspartate) receptor dysfunction is widely implicated in pathophysiology of autism spectrum disorder (ASD), a neurodevelopmental condition with a strong genetic basis. Here we investigated heterozygous mouse mutants carrying the ASD-linked C456Y mutation of Grin2b, a high-confidence ASD risk gene encoding the GluN2B subunit of the NMDA receptors. Comprehensive transcriptomic analyses across multiple brain regions and postnatal ages revealed large-scale gene expression changes, particularly in pathways related to oxidative phosphorylation and ribosome/translation, suggesting brain-wide alteration of energy metabolism and protein synthesis in Grin2b+/C456Y mice. Starting from transcriptomic evidence, we additionally discovered widespread splicing abnormalities, and impaired hippocampal neurogenesis in Grin2b mutants. Interestingly, the underlying genes and the spatial and temporal patterns of transcriptomic changes in Grin2b+/C456Y mice differed substantially from those observed in mutant mice lacking Grin2a, which encodes the GluN2A subunit of the NMDA receptor but is a schizophrenia risk gene. These findings underscore the distinct role of Grin2b in brain development and function and reveal potential mechanisms by which Grin2b loss of function may lead to neurodevelopmental disorders.
2026-01-07 | GSE306925 | GEO
Project description:NMDA (N-methyl-d-aspartate) receptor dysfunction is widely implicated in pathophysiology of autism spectrum disorder (ASD), a neurodevelopmental condition with a strong genetic basis. Here we investigated heterozygous mouse mutants carrying the ASD-linked C456Y mutation of Grin2b, a high-confidence ASD risk gene encoding the GluN2B subunit of the NMDA receptors. Comprehensive transcriptomic analyses across multiple brain regions and postnatal ages revealed large-scale gene expression changes, particularly in pathways related to oxidative phosphorylation and ribosome/translation, suggesting brain-wide alteration of energy metabolism and protein synthesis in Grin2b+/C456Y mice. Starting from transcriptomic evidence, we additionally discovered widespread splicing abnormalities, and impaired hippocampal neurogenesis in Grin2b mutants. Interestingly, the underlying genes and the spatial and temporal patterns of transcriptomic changes in Grin2b+/C456Y mice differed substantially from those observed in mutant mice lacking Grin2a, which encodes the GluN2A subunit of the NMDA receptor but is a schizophrenia risk gene. These findings underscore the distinct role of Grin2b in brain development and function and reveal potential mechanisms by which Grin2b loss of function may lead to neurodevelopmental disorders.
2026-01-07 | GSE306924 | GEO
Project description:NMDA (N-methyl-d-aspartate) receptor dysfunction is widely implicated in pathophysiology of autism spectrum disorder (ASD), a neurodevelopmental condition with a strong genetic basis. Here we investigated heterozygous mouse mutants carrying the ASD-linked C456Y mutation of Grin2b, a high-confidence ASD risk gene encoding the GluN2B subunit of the NMDA receptors. Comprehensive transcriptomic analyses across multiple brain regions and postnatal ages revealed large-scale gene expression changes, particularly in pathways related to oxidative phosphorylation and ribosome/translation, suggesting brain-wide alteration of energy metabolism and protein synthesis in Grin2b+/C456Y mice. Starting from transcriptomic evidence, we additionally discovered widespread splicing abnormalities, and impaired hippocampal neurogenesis in Grin2b mutants. Interestingly, the underlying genes and the spatial and temporal patterns of transcriptomic changes in Grin2b+/C456Y mice differed substantially from those observed in mutant mice lacking Grin2a, which encodes the GluN2A subunit of the NMDA receptor but is a schizophrenia risk gene. These findings underscore the distinct role of Grin2b in brain development and function and reveal potential mechanisms by which Grin2b loss of function may lead to neurodevelopmental disorders.
2026-01-07 | GSE312325 | GEO
Project description:Aberrant mRNA Splicing and Impaired Hippocampal Neurogenesis in Grin2b Mutant Mice
| PRJNA1376138 | ENA
Project description:Aberrant mRNA Splicing and Impaired Hippocampal Neurogenesis in Grin2b Mutant Mice [RNAseq]
| PRJNA1373027 | ENA
Project description:Aberrant mRNA Splicing and Impaired Hippocampal Neurogenesis in Grin2b Mutant Mice [grin2b_bulkRNAseq]
| PRJNA1313932 | ENA
Project description:Aberrant mRNA Splicing and Impaired Hippocampal Neurogenesis in Grin2b Mutant Mice [grin2b_snRNAseq]
| PRJNA1313934 | ENA
Project description:Stroke significantly stimulates neurogenesis in the adult dentate gyrus, though the functional role of this postlesional response is mostly unclear. Recent findings suggest that newborn neurons generated in the context of stroke may fail to correctly integrate into pre-existing networks. We hypothesized that increased neurogenesis in the dentate gyrus following stroke is associated with aberrant neurogenesis and impairment of hippocampus-dependent memory. To address these questions we used the middle cerebral artery occlusion model (MCAO) in mice. Animals were housed either under standard conditions or with free access to running wheels. Newborn granule cells were labelled with the thymidine analoque EdU and retroviral vectors. To assess memory performance, we employed a modified version of the Morris water maze (MWM) allowing differentiation between hippocampus dependent and independent learning strategies. Newborn neurons were morphologically analyzed using confocal microscopy and Neurolucida system at 7 weeks. We found that neurogenesis was significantly increased following MCAO. Animals with MCAO needed more time to localize the platform and employed less hippocampus-dependent search strategies in MWM versus controls. Confocal studies revealed an aberrant cell morphology with basal dendrites and an ectopic location (e.g. hilus) of new granule cells born in the ischemic brain. Running increased the number of new neurons but also enhanced aberrant neurogenesis. Running, did not improve the general performance in the MWM but slightly promoted the application of precise spatial search strategies. In conclusion, ischemic insults cause hippocampal-dependent memory deficits which are associated with aberrant neurogenesis in the dentate gyrus indicating ischemia-induced maladaptive plasticity in the hippocampus.
| S-EPMC5598932 | biostudies-literature
Project description:Patients with epilepsy are at high risk for major depression relative to the general population, and both disorders are associated with changes in adult hippocampal neurogenesis, although the mechanisms underlying disease onset remain unknown. The expression of fosB, an immediate early gene encoding FosB and ?FosB/?2?FosB by alternative splicing and translation initiation, is known to be induced in neural progenitor cells within the subventricular zone of the lateral ventricles and subgranular zone of the hippocampus, following transient forebrain ischemia in the rat brain. Moreover, adenovirus-mediated expression of fosB gene products can promote neural stem cell proliferation. We recently found that fosB-null mice show increased depressive behavior, suggesting impaired neurogenesis in fosB-null mice. In the current study, we analyzed neurogenesis in the hippocampal dentate gyrus of fosB-null and fosB(d/d) mice that express ?FosB/?2?FosB but not FosB, in comparison with wild-type mice, alongside neuropathology, behaviors, and gene expression profiles. fosB-null but not fosB(d/d) mice displayed impaired neurogenesis in the adult hippocampus and spontaneous epilepsy. Microarray analysis revealed that genes related to neurogenesis, depression, and epilepsy were altered in the hippocampus of fosB-null mice. Thus, we conclude that the fosB-null mouse is the first animal model to provide a genetic and molecular basis for the comorbidity between depression and epilepsy with abnormal neurogenesis, all of which are caused by loss of a single gene, fosB.
| S-EPMC3672000 | biostudies-literature
Project description:Prolonged seizures can disrupt stem cell behavior in the adult hippocampus, an important brain structure for spatial memory. Here, using a mouse model of pilocarpine-induced status epilepticus (SE), we characterized spatiotemporal expression of Lin28a mRNA and proteins after SE. Unlike Lin28a transcripts, induction of LIN28A protein after SE was detected mainly in the subgranular zone, where immunoreactivity was found in progenitors, neuroblasts, and immature and mature granule neurons. To investigate roles of LIN28A in epilepsy, we generated Nestin-Cre:Lin28aloxP/loxP (conditional KO [cKO]) and Nestin-Cre:Lin28a+/+ (WT) mice to block LIN28A upregulation in all neuronal lineages after acute seizure. Adult-generated neuron- and hippocampus-associated cognitive impairments were absent in epileptic LIN28A-cKO mice, as evaluated by pattern separation and contextual fear conditioning tests, respectively, while sham-manipulated WT and cKO animals showed comparable memory function. Moreover, numbers of hilar PROX1-expressing ectopic granule cells (EGCs), together with PROX1+/NEUN+ mature EGCs, were significantly reduced in epileptic cKO mice. Transcriptomics analysis and IHC validation at 3 days after pilocarpine administration provided potential LIN28A downstream targets such as serotonin receptor 4. Collectively, our findings indicate that LIN28A is a potentially novel target for regulation of newborn neuron-associated memory dysfunction in epilepsy by modulating seizure-induced aberrant neurogenesis.
| S-EPMC10906464 | biostudies-literature