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Project description:The RecQ helicase family plays a vital role in maintaining genome stability, including DNA replication, recombination, and DNA repair. In human cells, there are five RecQ helicases: RECQL1, Bloom syndrome (BLM), Werner syndrome (WRN), RECQL4, and RECQL5. Dysfunction or absence of RecQ proteins is associated with genetic disorders, tumorigenesis, premature aging, and neurodegeneration. The biological importance of RecQ helicases is well established; However, it is still unknown the potential outcomes after DNA damage, and there is no systematic study yet to compare the behavioral changes amongst various RecQ-deficient mice. In this study, we investigated the effects of IR treatment on three RecQ-deficient mouse models (Recql1, Wrn and Recql4). Here we provided evidence that RecQ dysfunction impaired social ability and induced depressive-like behavior in mice, with or without irradiation stress, while abnormal cognitive behaviors only existed in RecQ-deficient mice without IR treatment, suggesting RecQ proteins contribute to mood and cognition. Furthermore, transcripts and metabolomics analysis revealed significant alterations in the RecQ-deficient mice, especially after IR treatment. Particularly, pathways related to neuronal and microglia functions, DNA damage repair, cell cycle, and reactive oxygen response were downregulated in the RecQ4 and Wrn mice. In addition, increased DNA damage responses were found in RecQ-deficient mice. Notably, two genes, Aldolase Fructose-Bisphosphate B (Aldob) and NADPH Oxidase 4 (Nox4), were differentially expressed in RecQ-deficient mice. Our finding suggested that RecQ dysfunction contributes to social and depressive-like behaviors in mice, and that aldolase activity may be associated with these changes, representing it as a potential therapeutic intervention. To understand what metabolism-related gene expression changes are induced by γ-irradiation in the WT, RecQ1, WRN, RecQ4 deficient mice. They were exposed the whole body with γ-irradiation (IR, 6 Gy), thereafter prefrontal cortex tissues were collected from each mouse and subjected to RNA isolation.
2026-01-20 | GSE220633 | GEO
Project description:The RecQ helicase family plays a vital role in maintaining genome stability, including DNA replication, recombination, and DNA repair. In human cells, there are five RecQ helicases: RECQL1, Bloom syndrome (BLM), Werner syndrome (WRN), RECQL4, and RECQL5. Dysfunction or absence of RecQ proteins is associated with genetic disorders, tumorigenesis, premature aging, and neurodegeneration. The biological importance of RecQ helicases is well established; However, it is still unknown the potential outcomes after DNA damage, and there is no systematic study yet to compare the behavioral changes amongst various RecQ-deficient mice. In this study, we investigated the effects of IR treatment on three RecQ-deficient mouse models (Recql1, Wrn and Recql4). Here we provided evidence that RecQ dysfunction impaired social ability and induced depressive-like behavior in mice, with or without irradiation stress, while abnormal cognitive behaviors only existed in RecQ-deficient mice without IR treatment, suggesting RecQ proteins contribute to mood and cognition. Furthermore, transcripts and metabolomics analysis revealed significant alterations in the RecQ-deficient mice, especially after IR treatment. Particularly, pathways related to neuronal and microglia functions, DNA damage repair, cell cycle, and reactive oxygen response were downregulated in the RecQ4 and Wrn mice. In addition, increased DNA damage responses were found in RecQ-deficient mice. Notably, two genes, Aldolase Fructose-Bisphosphate B (Aldob) and NADPH Oxidase 4 (Nox4), were differentially expressed in RecQ-deficient mice. Our finding suggested that RecQ dysfunction contributes to social and depressive-like behaviors in mice, and that aldolase activity may be associated with these changes, representing it as a potential therapeutic intervention. To understand what Neuroinflammation-related gene expression changes are induced by γ-irradiation in the WT, RecQ1, WRN, RecQ4 deficient mice. They were exposed the whole body with γ-irradiation (IR, 6 Gy), thereafter prefrontal cortex tissues were collected from each mouse and subjected to RNA isolation.
2026-01-20 | GSE220636 | GEO
Project description:RecQ dysfunction contributes to social and depressive-like behavior and aldolase activity changes in mice
| PRJNA910562 | ENA
Project description:RecQ dysfunction contributes to social and depressive-like behavior and aldolase activity changes in mice [Metabolic]
| PRJNA910564 | ENA
Project description:RECQL dysfunction contributes to social and depressive-like behavior and aldolase activity changes in mice [Neuroinflammation]
| PRJNA910657 | ENA
Project description:BackgroundMajor depressive disorder (MDD) is a common but severe psychiatric illness characterized by depressive mood and diminished interest. Both nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 1 (NLRP1) inflammasome and autophagy have been reported to implicate in the pathological processes of depression. However, the mechanistic interplay between NLRP1 inflammasome, autophagy, and depression is still poorly known.MethodsAnimal model of depression was established by chronic social defeat stress (CSDS). Depressive-like behaviors were determined by social interaction test (SIT), sucrose preference test (SPT), open field test (OFT), forced swim test (FST), and tail-suspension test (TST). The protein expression levels of NLRP1 inflammasome complexes, pro-inflammatory cytokines, phosphorylated-phosphatidylinositol 3-kinase (p-PI3K)/PI3K, phosphorylated-AKT (p-AKT)/AKT, phosphorylated-mechanistic target of rapamycin (p-mTOR)/mTOR, brain-derived neurotrophic factor (BDNF), phosphorylated-tyrosine kinase receptor B (p-TrkB)/TrkB, Bcl-2-associated X protein (Bax)/B-cell lymphoma-2 (Bcl2) and cleaved cysteinyl aspartate-specific proteinase-3 (caspase-3) were examined by western blotting. The mRNA expression levels of pro-inflammatory cytokines were tested by quantitative real-time PCR. The interaction between proteins was detected by immunofluorescence and coimmunoprecipitation. Neuronal injury was assessed by Nissl staining. The autophagosomes were visualized by transmission electron microscopy. Nlrp1a knockdown was performed using an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion.ResultsCSDS exposure caused a bidirectional change in hippocampal autophagy function, which was activated in the initial period but impaired at the later stage. In addition, CSDS exposure increased the expression levels of hippocampal NLRP1 inflammasome complexes, pro-inflammatory cytokines, p-PI3K, p-AKT and p-mTOR in a time-dependent manner. Interestingly, NLRP1 is immunoprecipitated with mTOR but not PI3K/AKT and CSDS exposure facilitated the immunoprecipitation between them. Hippocampal Nlrp1a knockdown inhibited the activity of PI3K/AKT/mTOR signaling, rescued the impaired autophagy and ameliorated depressive-like behavior induced by CSDS. In addition, rapamycin, an autophagy inducer, abolished NLRP1 inflammasome-driven inflammatory reactions, alleviated depressive-like behavior and exerted a neuroprotective effect.ConclusionsAutophagy dysfunction contributes to NLRP1 inflammasome-linked depressive-like behavior in mice and the regulation of autophagy could be a valuable therapeutic strategy for the management of depression.
| S-EPMC10765763 | biostudies-literature
Project description:We report here hippocampal RNA-seq data from adult (20 weeks) male offspring exposed to 0 mg (control) or 50 mg BPA/kg diet during gestation and lactation.
2018-06-19 | GSE102849 | GEO
Project description:Fetal exposure to endocrine disrupting chemicals (EDCs) has been associated with adverse neurobehavioral outcomes across the lifespan and can persist across multiple generations of offspring. However, the underlying mechanisms driving these changes are not well understood. We investigated the molecular perturbations associated with EDC-induced behavioral changes in first (F1) and second (F2) filial generations, using the model EDC bisphenol A (BPA). C57BL/6J dams were exposed to BPA from preconception until lactation through the diet at doses (10 μg/kg bw/d-lower dose or 10 mg/kg bw/d-upper dose) representative of human exposure levels. As adults, F1 male offspring exhibited increased depressive-like behavior, measured by the forced swim test, while females were unaffected. These behavioral changes were limited to the F1 generation and were not associated with altered maternal care. Transcriptome analysis by RNA-sequencing in F1 control and upper dose BPA-exposed adult male hippocampus revealed neurotransmitter systems as major pathways disrupted by developmental BPA exposure. High performance liquid chromatography demonstrated a male-specific reduction in hippocampal serotonin. Administration of the selective serotonin reuptake inhibitor fluoxetine (20 mg/kg bw) rescued the depressive-like phenotype in males exposed to lower, but not upper, dose BPA, suggesting distinct mechanisms of action for each exposure dose. Finally, high resolution mass spectrometry revealed reduced circulating levels of the neuroactive steroid dehydroepiandrosterone in BPA-exposed males, suggesting another potential mechanism underlying the depressive-like phenotype. Thus, behavioral changes associated with early life BPA exposure may be mediated by sex-specific disruptions in the serotonergic system and/or sex steroid biogenesis in male offspring.
| S-EPMC6261494 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-06-14 | GSE217619 | GEO
Project description:Autophagy is a lysosomal degradation pathway that regulates cellular homeostasis. It is constitutively active in neurons and controls the essential steps of neuronal development, leading to its dysfunction in neurodevelopmental disorders. Although mTOR-associated impaired autophagy has previously been reported in neurodevelopmental disorders, there is lack of information about the dysregulation of mTOR-independent autophagy in neurodevelopmental disorders. In this study, we investigated whether the loss of Epac2, involved in the mTOR-independent pathway, affects autophagy activity and whether the activity of autophagy is associated with social-behavioral phenotypes in mice with Epac2 deficiencies. We observed an accumulation of autophagosomes and a significant increase in autophagic flux in Epac2-deficient neurons, which had no effect on mTOR activity. Next, we examined whether an increase in autophagic activity contributed to the social behavior exhibited in Epac2-/- mice. The social recognition deficit observed in Epac2-/- mice recovered in double transgenic Epac2-/-: Atg5+/- mice. Our study suggests that excessive autophagy due to Epac2 deficiencies may contribute to social recognition defects through an mTOR-independent pathway.
| S-EPMC8240198 | biostudies-literature