{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307928/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307928"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Multi-modal transcriptomic analysis reveals conserved and divergent molecular mechanisms underlying behaviors in mouse models of schizophrenia","description":"Schizophrenia (SCZ) is a severe mental disorder with complex behavioral pathology and complex genetic risk. Here, we performed an integrated transcriptomic analysis of the prefrontal cortex in two distinct male C57BL/6 mouse models of schizophrenia, the neurodevelopmental methylazoxymethanol acetate (MAM) model and the acute non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist MK-801 model, compared to that of human patients. Transcriptome in the MK-801 model displayed a modest correlation with that of schizophrenia patients, higher than the MAM model, underscoring NMDAR antagonism's relevance to the core pathology of the disorder. Using weighted gene co-expression network analysis, we identified fifteen co-expression modules across the mouse models, with eight modules significantly associated with schizophrenia-like behavioral endophenotypes. Notably, modules darkturquoise (linked to hyperlocomotion) and royalblue (associated with social withdrawal) were enriched in Wnt and PI3K/Akt signaling pathways, respectively. Pharmacological inhibition of these two pathways specifically rectified corresponding behavioral anomalies in the MK-801 model, highlighting the critical role of altered Wnt and PI3K/Akt signaling in these behavioral domains of schizophrenia-related behaviors and proposing new avenues for therapeutic intervention.","dates":{"publication":"2026/09/11"},"accession":"GSE307928","cross_references":{"GSM":["GSM9234098","GSM9234095","GSM9234094","GSM9234097","GSM9234096","GSM9234093","GSM9234092"],"GPL":["34290"],"GSE":["307928"],"taxon":["Mus musculus"]}}