Brain transcriptome analysis of Arid1b heterozygote mutation and long-lasting effects of early chronic fluoxetine treatment for mutant mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE203344 | GEO | 2022/07/21
REPOSITORIES: GEO
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Project description:Arid1b is a chromatin remodeler implicated in neurodevelopmental disorders. Arid1b mutant mice with haploinsufficiency (Arid1b HT) displayed persistent excitatory synaptic dysfunction from juvenile to adult stage, decreased synaptic density and transmission. Moreover, they showed autistic-like behaviors in both of early and adult stages, decreased sociability in pup USV calling and adult social interaction, and adult repetitive grooming. To investigate early transcriptomic changes in Arid1b mutant mice, RNAseq analysis of whole brain from wild-type and Arid1b mutant mice at postnatal day 10 was done. Transcriptomic changes support these electrophysiological and behavioral deficits. Arid1b HT mice at postnatal day 10 showed alterations in genes implicated in synaptic functions and ASD. Next, we found that early chronic fluoxetine treatment could carry out long-lasting restoration in electrophysiological and behavioral deficits in Arid1b HT mice. Whole brain transcriptomic analysis with mice at postnatal day 120 which underwent chronic fluoxetine treatment from postnatal day 3 to postnatal day 21 via mammillary milk was done to figure out transcriptomic reprogramming which contributes to this restoration. Comparing fluoxetine treated Arid1b HT mice and vehicle group, fluoxetine treated mice showed upregulation of synapse-related genes and disease related gene sets with reverse-ASD directions.
2022-07-21 | GSE189653 | GEO
Project description:Brain transcriptome analysis of Arid1b heterozygote mutation and long-lasting effects of early chronic fluoxetine treatment for mutant mice
| PRJNA839595 | ENA
Project description:Brain transcriptome analysis of Arid1b heterozygote mutation and long-lasting effects of early chronic fluoxetine treatment for mutant mice [RNA-Seq]
| PRJNA783991 | ENA
Project description:Arid1b is a chromatin remodeler implicated in neurodevelopmental disorders. Arid1b mutant mice with haploinsufficiency (Arid1b HT) displayed persistent excitatory synaptic dysfunction from juvenile to adult stage, decreased synaptic density and transmission. Moreover, they showed autistic-like behaviors in both of early and adult stages, decreased sociability in pup USV calling and adult social interaction, and adult repetitive grooming. To investigate pup stage transcriptomic changes in Arid1b mutant mice, RNAseq analysis of whole brain from wild-type and Arid1b mutant mice at postnatal day 3 was done. Transcriptomic changes support these electrophysiological and behavioral deficits. Arid1b HT mice at postnatal day 3 showed alterations in genes implicated in synaptic functions and ASD.
2022-07-21 | GSE203214 | GEO
Project description:Arid1b is a chromatin remodeler implicated in neurodevelopmental disorders. Arid1b mutant mice with haploinsufficiency (Arid1b HT) displayed persistent excitatory synaptic dysfunction from juvenile to adult stage, decreased synaptic density and transmission. Moreover, they showed autistic-like behaviors in both of early and adult stages, decreased sociability in pup USV calling and adult social interaction, and adult repetitive grooming. To investigate early transcriptomic changes in Arid1b mutant mice, RNAseq analysis of prefrontal cortex from wild-type and Arid1b mutant mice at postnatal day 10 was done. Transcriptomic changes support these electrophysiological and behavioral deficits. Arid1b HT mice at postnatal day 10 showed alterations in genes implicated in synaptic functions and ASD.
2022-07-21 | GSE203249 | GEO
Project description:Whole-brain transcriptome of Arid1b heterozygote mutation mice age of postnatal day 3
| PRJNA839057 | ENA
Project description:Chronic treatment with antidepressants increases neurogenesis in the adult hippocampus. This increase in the production of new neurons may be required for the behavioral effects of antidepressants. However, it is not known which class of cells within the neuronal differentiation cascade is targeted by the drugs. We have generated a reporter mouse line, which allows identification and classification of early neuronal progenitors. It also allows accurate quantitation of changes induced by neurogenic agents in these distinct subclasses of neuronal precursors. We use this line to demonstrate that the selective serotonin reuptake inhibitor antidepressant fluoxetine does not affect division of stem-like cells in the dentate gyrus but increases symmetric divisions of an early progenitor cell class. We further demonstrate that these cells are the sole class of neuronal progenitors targeted by fluoxetine in the adult brain and suggest that the fluoxetine-induced increase in new neurons arises as a result of the expansion of this cell class. This finding defines a cellular target for antidepressant drug therapies.
| S-EPMC1461404 | biostudies-literature
Project description:Chronic stress triggers rigorous psychological and physiological changes, including immunological system adaptations. However, the effects of long-term social restriction on human immune system have not been investigated. The present study is to investigate the effect of chronic stress on immune changes in human blood, with the stress stimuli controlled.10 male volunteers were group isolated from the modern society in a 50-meter-square room for 150 days, with enriched nutrition and good living conditions provided. Serum examination of immune system markers demonstrated numerous changes in different aspects of the immune functions. The changes were observed as early as 30 days and could last for another 150 days after the termination of the restriction period (300 days' time point). The results strongly argued for the adaptation of immunological system under chronic social restriction stress in adult human, preceding a clear change in psychological conditions. The changes of these immune system factors could as well act as the serum biomarkers in clinical early-diagnosis of stress-related disorders.
| S-EPMC5464898 | biostudies-other
Project description:BACKGROUND: Fluoxetine, a selective serotonin reuptake inhibitor, is approved for treatment of childhood depression. In rats, fluoxetine influences neuronal development, but it is unclear whether it also influences glia development. S100B is a glia-derived calcium-binding protein, which may influence the development of serotonergic fibers and, vice versa, serotonin may influence the expression of S100B. OBJECTIVES: The purpose of this study was to investigate whether fluoxetine treatment influences the expression of S100B during postnatal development, and whether potential changes are regionally dependent upon the time frame of drug administration. METHODS: S100B gene expression and S100B protein expression in three different brain regions (frontal cortex, hippocampus, and striatum) were studied by real-time polymerase chain reaction (PCR) and immunohistochemistry, respectively. First, a short-term effect, 24 hours after a 14 day fluoxetine treatment (5 mg/kg/bw s.c.) of rats either from postnatal day (PD) 1 to 15, 21 to 35, or 50 to 64, was investigated. Then, the same treatment was used to analyze S100B gene and protein levels at PD 90 (long-term effect). RESULTS: At PD 90, a significant increase of gene and protein expression was observed in all regions if rats were treated during PDs 21-35, whereas treatment during other periods had no long-term effects. A short-term effect 24 hours after fluoxetine treatment was found for almost all development stages and regions, demonstrated by a significant increase of S100B. CONCLUSIONS: These results support recent research indicating a highly drug-sensitive period (i.e., periadolescence) of rat brain development. Therefore, further clinical studies should be performed to clarify whether such a sensitive period also exists in children.
| S-EPMC3779020 | biostudies-literature
Project description:Recent studies have revealed that ARID1A, encoding AT-rich interactive domain 1A (SWI-like), is frequently mutated across a variety of human cancers and also has bona fide tumor suppressor properties. Consequently, identification of vulnerabilities conferred by ARID1A mutation would have major relevance for human cancer. Here, using a broad screening approach, we identify ARID1B, an ARID1A homolog whose gene product is mutually exclusive with ARID1A in SWI/SNF complexes, as the number 1 gene preferentially required for the survival of ARID1A-mutant cancer cell lines. We show that loss of ARID1B in ARID1A-deficient backgrounds destabilizes SWI/SNF and impairs proliferation in both cancer cells and primary cells. We also find that ARID1A and ARID1B are frequently co-mutated in cancer but that ARID1A-deficient cancers retain at least one functional ARID1B allele. These results suggest that loss of ARID1A and ARID1B alleles cooperatively promotes cancer formation but also results in a unique functional dependence. The results further identify ARID1B as a potential therapeutic target for ARID1A-mutant cancers.
| S-EPMC3954704 | biostudies-literature