{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ramos A"],"funding":["U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)","NIMH NIH HHS","NARSAD, Stanley, and S-R/RUSK","U.S. Department of Health & Human Services | NIH | National Institute of Mental Health"],"pagination":["2967-2978"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11449656"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["29(10)"],"pubmed_abstract":["We report a mechanism that underlies stress-induced cognitive inflexibility at the molecular level. In a mouse model under subacute cellular stress in which deficits in rule shifting tasks were elicited, the nuclear glyceraldehyde dehydrogenase (N-GAPDH) cascade was activated specifically in microglia in the prelimbic cortex. The cognitive deficits were normalized with a pharmacological intervention with a compound (the RR compound) that selectively blocked the initiation of N-GAPDH cascade without affecting glycolytic activity. The normalization was also observed with a microglia-specific genetic intervention targeting the N-GAPDH cascade. At the mechanistic levels, the microglial secretion of High-Mobility Group Box (HMGB), which is known to bind with and regulate the NMDA-type glutamate"],"journal":["Molecular psychiatry"],"pubmed_title":["Nuclear GAPDH in cortical microglia mediates cellular stress-induced cognitive inflexibility."],"pmcid":["PMC11449656"],"funding_grant_id":["MH-107730","MH-105660","MH-094268 Silvio O. Conte center","P50 MH094268","R01 MH105660","R01 MH107730"],"pubmed_authors":["Tsujimura T","Palen T","Saitoh T","Namkung H","Sawa A","Zhang M","Carloni E","Niwa M","Takimoto E","Calva C","Ishizuka K","Srivastava R","Slusher BS","Kariya T","Ramos A","Hayashida A","Ikemoto S","Hayes LN","Elkins N","Rais R","Saito A"],"additional_accession":[]},"is_claimable":false,"name":"Nuclear GAPDH in cortical microglia mediates cellular stress-induced cognitive inflexibility.","description":"We report a mechanism that underlies stress-induced cognitive inflexibility at the molecular level. In a mouse model under subacute cellular stress in which deficits in rule shifting tasks were elicited, the nuclear glyceraldehyde dehydrogenase (N-GAPDH) cascade was activated specifically in microglia in the prelimbic cortex. The cognitive deficits were normalized with a pharmacological intervention with a compound (the RR compound) that selectively blocked the initiation of N-GAPDH cascade without affecting glycolytic activity. The normalization was also observed with a microglia-specific genetic intervention targeting the N-GAPDH cascade. At the mechanistic levels, the microglial secretion of High-Mobility Group Box (HMGB), which is known to bind with and regulate the NMDA-type glutamate","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Oct","modification":"2025-04-22T21:40:56.737Z","creation":"2025-04-06T03:42:22.118Z"},"accession":"S-EPMC11449656","cross_references":{"pubmed":["38615102"],"doi":["10.1038/s41380-024-02553-1"]}}