American Journal of Medical Genetics Part B: Neuropsychiatric Genetics最新文献

{"title":"ADHD-associated PARK2 copy number variants: A pilot study on gene expression and effects of supplementary deprivation in patient-derived cell lines","authors":"Franziska Radtke,&nbsp;Viola Stella Palladino,&nbsp;Rhiannon V. McNeill,&nbsp;Andreas G. Chiocchetti,&nbsp;Denise Haslinger,&nbsp;Matthias Leyh,&nbsp;Danijel Gersic,&nbsp;Markus Frank,&nbsp;Lena Grünewald,&nbsp;Stephan Klebe,&nbsp;Oliver Brüstle,&nbsp;Katharina Günther,&nbsp;Frank Edenhofer,&nbsp;Thorsten M. Kranz,&nbsp;Andreas Reif,&nbsp;Sarah Kittel-Schneider","doi":"10.1002/ajmg.b.32918","DOIUrl":"10.1002/ajmg.b.32918","url":null,"abstract":"<p>Recent studies show an association of Parkin RBR E3 ubiquitin protein ligase (<i>PARK2</i>) copy number variations (CNVs) with attention deficit hyperactivity disorder (ADHD). The aim of our pilot study to investigate gene expression associated with <i>PARK2</i> CNVs in human-derived cellular models. We investigated gene expression in fibroblasts, hiPSC and dopaminergic neurons (DNs) of ADHD <i>PARK2</i> deletion and duplication carriers by qRT PCR compared with healthy and ADHD cell lines without <i>PARK2</i> CNVs. The selected 10 genes of interest were associated with oxidative stress response (<i>TP53, NQO1,</i> and <i>NFE2L2</i>), ubiquitin pathway (<i>UBE3A, UBB, UBC,</i> and <i>ATXN3</i>) and with a function in mitochondrial quality control (<i>PINK1, MFN2,</i> and <i>ATG5</i>). Additionally, an exploratory RNA bulk sequencing analysis in DNs was conducted. Nutrient deprivation as a supplementary deprivation stress paradigm was used to enhance potential genotype effects. At baseline, in fibroblasts, hiPSC, and DNs, there was no significant difference in gene expression after correction for multiple testing. After nutrient deprivation in fibroblasts NAD(P)H-quinone-dehydrogenase 1 (<i>NQO1</i>) expression was significantly increased in <i>PARK2</i> CNV carriers. In a multivariate analysis, ubiquitin C (<i>UBC</i>) was significantly upregulated in fibroblasts of <i>PARK2</i> CNV carriers. RNA sequencing analysis of DNs showed the strongest significant differential regulation in Neurontin (<i>NNAT</i>) at baseline and after nutrient deprivation. Our preliminary results suggest differential gene expression in pathways associated with oxidative stress, ubiquitine-proteasome, immunity, inflammation, cell growth, and differentiation, excitation/inhibition modulation, and energy metabolism in <i>PARK2</i> CNV carriers compared to wildtype healthy controls and ADHD patients.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"189 7-8","pages":"257-270"},"PeriodicalIF":2.8,"publicationDate":"2022-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.32918","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9189804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-sectional and longitudinal associations between gut microbiota composition and cognition in the second year of life: Findings from the Child Health and Resident Microbes study","authors":"Misa Matsuyama,&nbsp;Nida Murtaza,&nbsp;Mark Morrison,&nbsp;Peter S.W. Davies,&nbsp;Rebecca J. Hill,&nbsp;Amy Loughman","doi":"10.1002/ajmg.b.32915","DOIUrl":"10.1002/ajmg.b.32915","url":null,"abstract":"<p>The relationship between the gut microbiota and brain function are receiving increasing research attention. Studies investigating gut microbiota and early childhood neurocognition are limited, particularly in longitudinal measurements. We examined cross-sectional relationships between gut microbiota of a cohort of otherwise healthy children using 16S rRNA sequencing and their cognitive development measured with Bayley's Scales of Infant Development III at 24 months of age (<i>n</i> = 43), and longitudinal relationships between gut microbiota composition at 12 months (<i>n</i> = 41) of age and neurodevelopment at 24 months of age. Associations between gut microbiota characteristics and cognitive development were observed both cross-sectionally and longitudinally, notably with butyrate producing bacteria among some children. Bacterial diversity varied between cross-sectional and longitudinal observations, where the gut microbiota community of children with lower cognitive scores had a trend toward higher alpha diversity, whereas, in the longitudinal observation, a trend toward reduced alpha diversity was observed. This study is limited by a small sample size and its exploratory nature. Yet, the study contributes to knowledge in the gut microbiota characteristics and early life neurodevelopment, a field of study which is underexplored, presenting opportunities for future larger specific studies.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"189 7-8","pages":"285-292"},"PeriodicalIF":2.8,"publicationDate":"2022-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.32915","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88393747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CELSR1 variants are associated with partial epilepsy of childhood","authors":"Zheng Chen,&nbsp;Sheng Luo,&nbsp;Zhi-Gang Liu,&nbsp;Yan-Chun Deng,&nbsp;Su-Li He,&nbsp;Xiao-Rong Liu,&nbsp;Yong-Hong Yi,&nbsp;Jie Wang,&nbsp;Liang-Di Gao,&nbsp;Bing-Mei Li,&nbsp;Zhi-Jun Wu,&nbsp;Zi-Long Ye,&nbsp;De-Hai Liang,&nbsp;Wen-Jun Bian,&nbsp;Wei-Ping Liao,&nbsp;For the China Epilepsy Gene 1.0 Project","doi":"10.1002/ajmg.b.32916","DOIUrl":"10.1002/ajmg.b.32916","url":null,"abstract":"<p><i>CELSR1</i> gene, encoding cadherin EGF LAG seven-pass G-type receptor 1, is mainly expressed in neural stem cells during the embryonic period. It plays an important role in neurodevelopment. However, the relationship between <i>CELSR1</i> and disease of the central nervous system has not been defined. In this study, we performed trios-based whole-exome sequencing in a cohort of 356 unrelated cases with partial epilepsy without acquired causes and identified <i>CELSR1</i> variants in six unrelated cases. The variants included one de novo heterozygous nonsense variant, one de novo heterozygous missense variant, and four compound heterozygous missense variants that had one variant was located in the extracellular region and the other in the cytoplasm. The patients with biallelic variants presented severe epileptic phenotypes, whereas those with heterozygous variants were associated with a mild epileptic phenotype of benign epilepsy with centrotemporal spikes (BECTS). These variants had no or low allele frequency in the gnomAD database. The frequencies of the <i>CELSR1</i> variants in this cohort were significantly higher than those in the control populations. The evidence from ClinGen Clinical-Validity Framework suggested a strong association between <i>CELSR1</i> variants and epilepsy. These findings provide evidence that <i>CELSR1</i> is potentially a candidate pathogenic gene of partial epilepsy of childhood.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"189 7-8","pages":"247-256"},"PeriodicalIF":2.8,"publicationDate":"2022-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10638384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover Image, Volume 189B, Number 6, September 2022","authors":"","doi":"10.1002/ajmg.b.32856","DOIUrl":"https://doi.org/10.1002/ajmg.b.32856","url":null,"abstract":"","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2022-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44635883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ludvig Dahl's psychiatric genetic studies in his 1859 monograph: “Contribution to the knowledge of insanity in Norway”","authors":"Kenneth S. Kendler MD,&nbsp;Nikolai Czajkowski PhD,&nbsp;Ted Reichborn-Kjennerud MD, PhD","doi":"10.1002/ajmg.b.32914","DOIUrl":"10.1002/ajmg.b.32914","url":null,"abstract":"<p>In 1859, Ludvig Dahl, a Norwegian alienist, wrote a rarely referenced book entitled “Contribution to The Knowledge of Insanity.” In it, he describes a highly innovative psychiatric genetics research project with severable notable features. First, while the vast majority of 19th century psychiatric genetic studies were based on asylum hospital records, Dahl did field work to find cases of mental illness in certain defined areas within Norway, using census data, key-informants, record reviews, and personal interviews especially of suspected affected individuals. Second, for the first time in the history of psychiatric genetics, and perhaps more broadly in medical genetics, Dahl studied and graphed extensive pedigrees covering up to seven generations demonstrating a high density of psychiatric illness. Third, he proposed and conducted the first controlled investigation of familial aggregation of insanity. A 126 member 5-generation pedigree that he studied contained 8 individuals with confirmed insanity compared to 16 cases in the remaining 2,974 individuals in the Parish, a relative risk of nearly 12. Dahl also noted the co-segregation within pedigrees of mental handicap, deaf-mutism, and insanity. He evaluated familial-environmental sources of familial aggregation and noted, among nonpsychotic family members in his pedigrees, personalities that might reflect a “disposition” to insanity.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"189 6","pages":"177-184"},"PeriodicalIF":2.8,"publicationDate":"2022-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40618902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative multi-omics analysis of genomic, epigenomic, and metabolomics data leads to new insights for Attention-Deficit/Hyperactivity Disorder","authors":"Nikki Hubers, F. Hagenbeek, R. Pool, S. Déjean, A. Harms, Peter J. Roetman, C. V. van Beijsterveldt, V. Fanos, E. Ehli, R. Vermeiren, M. Bartels, J. Hottenga, T. Hankemeier, J. van Dongen, D. Boomsma","doi":"10.1101/2022.07.21.22277887","DOIUrl":"https://doi.org/10.1101/2022.07.21.22277887","url":null,"abstract":"The evolving field of multi-omics combines data across omics levels and provides methods for simultaneous analysis. We integrated genomics (transmitted and non-transmitted polygenic scores), epigenomics and metabolomics data in a multi-omics framework to identify biomarkers for ADHD and investigated the connections among omics levels. We trained single- and multi-omics models to differentiate between cases and controls in 596 twins (cases=14.8%) from the Netherlands Twin Register (NTR) demonstrating reasonable in-sample prediction through cross-validation. Out-of-sample prediction in NTR participants (N=258, cases=14.3%) and in a clinical sample (N=145, cases=51%) did not perform well (range misclassification: 0.40-0.57). The multi-omics model selected 30 PGSs, 143 CpGs, and 90 metabolites. We confirmed previous associations with ADHD such as with glucocorticoid exposure and the transmembrane protein family TMEM, show that the DNA methylation of the MAD1L1 gene associated with ADHD has a relation with parental smoking behavior and present novel findings including associations between indirect genetic effects and CpGs of the STAP2 gene. The results highlighted connections between omics levels, with the strongest connections between indirect genetic effects, CpGs, and amino acid levels. Our study shows that multi-omics designs considering interrelated omics levels can help unravel the complex biology underlying ADHD.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"82 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2022-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89847504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phenome-wide association study of polygenic scores for attention deficit hyperactivity disorder across two genetic ancestries in electronic health record data","authors":"Maria Niarchou,&nbsp;Julia M. Sealock,&nbsp;Peter Straub,&nbsp;Sandra Sanchez-Roige,&nbsp;James S. Sutcliffe,&nbsp;Lea K. Davis","doi":"10.1002/ajmg.b.32911","DOIUrl":"10.1002/ajmg.b.32911","url":null,"abstract":"<p>Testing the association between genetic scores for Attention Deficit Hyperactivity Disorder (ADHD) and health conditions, can help us better understand its complex etiology. Electronic health records linked to genetic data provide an opportunity to test whether genetic scores for ADHD correlate with ADHD and additional health outcomes in a health care context across different age groups. We generated polygenic scores (ADHD-PGS) trained on summary statistics from the latest genome-wide association study of ADHD (<i>N</i> = 55,374) and applied them to genome-wide data from 12,383 unrelated individuals of African-American ancestry and 66,378 unrelated individuals of European ancestry from the Vanderbilt Biobank. Overall, only Tobacco use disorder (TUD) was associated with ADHD-PGS in the African-American ancestry group (Odds ratio [95% confidence intervals] = 1.23[1.16–1.31], <i>p</i> = 9.3 × 10⁻⁰⁹). Eighty-six phenotypes were associated with ADHD-PGS in the European ancestry individuals, including ADHD (OR[95%CIs] = 1.22[1.16–1.29], <i>p</i> = 3.6 × 10⁻¹⁰), and TUD (OR[95%CIs] = 1.22[1.19–1.25], <i>p</i> = 2.8 × 10⁻⁴⁶). We then stratified outcomes by age (ages 0–11, 12–18, 19–25, 26–40, 41–60, and 61–100). Our results suggest that ADHD polygenic scores are associated with ADHD diagnoses early in life and with an increasing number of health conditions throughout the lifespan (even in the absence of ADHD diagnosis). This study reinforces the utility of applying trait-specific PGSs to biobank data, and performing exploratory sensitivity analyses, to probe relationships among clinical conditions.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"189 6","pages":"185-195"},"PeriodicalIF":2.8,"publicationDate":"2022-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c8/21/AJMG-189-185.PMC9378640.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10686000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The shared genetic basis of mood instability and psychiatric disorders: A cross-trait genome-wide association analysis","authors":"Guy Hindley,&nbsp;Kevin S. O'Connell,&nbsp;Zillur Rahman,&nbsp;Oleksandr Frei,&nbsp;Shahram Bahrami,&nbsp;Alexey Shadrin,&nbsp;Margrethe C. Høegh,&nbsp;Weiqiu Cheng,&nbsp;Naz Karadag,&nbsp;Aihua Lin,&nbsp;Linn Rødevand,&nbsp;Chun C. Fan,&nbsp;Srdjan Djurovic,&nbsp;Trine V. Lagerberg,&nbsp;Anders M. Dale,&nbsp;Olav B. Smeland,&nbsp;Ole A. Andreassen","doi":"10.1002/ajmg.b.32907","DOIUrl":"10.1002/ajmg.b.32907","url":null,"abstract":"<p>Recent genome-wide association studies of mood instability (MOOD) have found significant positive genetic correlation with major depression (DEP) and weak correlations with other psychiatric disorders. We investigated the polygenic overlap between MOOD and psychiatric disorders beyond genetic correlation to better characterize putative shared genetic determinants. GWAS summary statistics for schizophrenia (SCZ, <i>n</i> = 105,318), bipolar disorder (BIP, <i>n</i> = 413,466), DEP (<i>n</i> = 450,619), attention-deficit hyperactivity disorder (ADHD, <i>n</i> = 53,293), and MOOD (<i>n</i> = 363,705) were analyzed using the bivariate causal mixture model and conjunctional false discovery rate methods. MOOD correlated positively with all psychiatric disorders, but with wide variation in strength (<i>r</i>_g = 0.10–0.62). Of 10.4 K genomic variants influencing MOOD, 4 K–9.4 K influenced psychiatric disorders. Furthermore, MOOD was jointly associated with DEP at 163 loci, SCZ at 110, BIP at 60 and ADHD at 25. Fifty-three jointly associated loci were overlapping across two or more disorders, seven of which had discordant effect directions on psychiatric disorders. Genes mapped to loci associated with MOOD and all four disorders were enriched in a single gene-set, “synapse organization.” The extensive polygenic overlap indicates shared molecular underpinnings across MOOD and psychiatric disorders. However, distinct patterns of genetic correlation and effect directions may relate to differences in the core clinical features of each disorder.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"189 6","pages":"207-218"},"PeriodicalIF":2.8,"publicationDate":"2022-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9541703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10841886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical, demographic, and genetic risk factors of treatment-attributed suicidality in >10,000 Australian adults taking antidepressants","authors":"Adrian I. Campos,&nbsp;Enda M. Byrne,&nbsp;Frank Iorfino,&nbsp;Chiara Fabbri,&nbsp;Ian B. Hickie,&nbsp;Cathryn M. Lewis,&nbsp;Naomi R. Wray,&nbsp;Sarah E. Medland,&nbsp;Miguel E. Rentería,&nbsp;Nicholas G. Martin","doi":"10.1002/ajmg.b.32913","DOIUrl":"10.1002/ajmg.b.32913","url":null,"abstract":"<p>Emergence of suicidal symptoms has been reported as a potential antidepressant adverse drug reaction. Identifying risk factors associated could increase our understanding of this phenomenon and stratify individuals at higher risk. Logistic regressions were used to identify risk factors of self-reported treatment-attributed suicidal ideation (TASI). We then employed classifiers to test the predictive ability of the variables identified. A TASI GWAS, as well as SNP-based heritability estimation, were performed. GWAS replication was sought from an independent study. Significant associations were found for age and comorbid conditions, including bipolar and personality disorders. Participants reporting TASI from one antidepressant were more likely to report TASI from other antidepressants. No genetic loci associated with TAS I (<i>p</i> &lt; 5e-8) were identified. Of 32 independent variants with suggestive association (<i>p</i> &lt; 1e-5), 27 lead SNPs were available in a replication dataset from the GENDEP study. Only one variant showed a consistent effect and nominal association in the independent replication sample. Classifiers were able to stratify non-TASI from TASI participants (AUC = 0.77) and those reporting treatment-attributed suicide attempts (AUC = 0.85). The pattern of TASI co-occurrence across participants suggest nonspecific factors underlying its etiology. These findings provide insights into the underpinnings of TASI and serve as a proof-of-concept of the use of classifiers for risk stratification.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"189 6","pages":"196-206"},"PeriodicalIF":2.8,"publicationDate":"2022-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9544797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40615322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FOXO4 alleviates hippocampal neuronal damage in epileptic mice via the miR-138-5p/ROCK2 axis","authors":"Xin Jin,&nbsp;Xingjuan Liao,&nbsp;Longfei Wu,&nbsp;Jianling Huang,&nbsp;Zhimin Li,&nbsp;Yali Li,&nbsp;Fan Guo","doi":"10.1002/ajmg.b.32904","DOIUrl":"10.1002/ajmg.b.32904","url":null,"abstract":"<p>Epilepsy (EP) is one of the most universal neurological disorders. This study investigated the mechanism of forkhead box protein O4 (FOXO4) on hippocampal neuronal damage in EP mice. Initially, the EP mouse model and the in vitro HT-22 cell model were established. EP seizures and neuronal damage in mice were assessed. FOXO4, microRNA (miR)-138-5p, and rho-associated coiled-coil containing protein kinase 2 (ROCK2) levels in hippocampal tissues or HT-22 cells were examined. The cell viability and apoptosis of HT-22 cells were determined. The concentrations of oxidative stress markers and the levels of inflammatory cytokines in hippocampal tissues or HT-22 cells were detected. We found that FOXO4 was poorly expressed in EP. FOXO4 overexpression alleviated hippocampal neuronal damage in EP mice and improved HT-22 cell viability and inhibited apoptosis, and decreased oxidative stress and inflammation in hippocampal tissue and HT-22 cells. The bindings of miR-138-5p to FOXO4 and ROCK2 were analyzed, which showed that FOXO4 promoted miR-138-5p via binding to the miR-138-5p promoter region, and miR-138-5p inhibited ROCK2 expression. Joint experiments showed that miR-138-5p suppression or ROCK2 overexpression reversed the alleviation of FOXO4 overexpression on hippocampal neuronal damage. FOXO4 inhibited ROCK2 expression via promoting miR-138-5p expression, thus alleviating hippocampal neuronal damage in EP mice.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"189 7-8","pages":"271-284"},"PeriodicalIF":2.8,"publicationDate":"2022-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10636042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}