{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Keramidis I"],"funding":["Natural Sciences and Engineering Research Council of Canada","Canada First Research Excellence Fund","Fondation de la famille Lemaire Research","Norampac Research","Fonds de recherche du Québec—Santé","Weston Brain Institute Transformation Research","Canadian Institutes of Health Research","CIHR","Canada Research Chair"],"pagination":["4903-4915"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10690023"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["146(12)"],"pubmed_abstract":["Disinhibition during early stages of Alzheimer's disease is postulated to cause network dysfunction and hyperexcitability leading to cognitive deficits. However, the underlying molecular mechanism remains unknown. Here we show that, in mouse lines carrying Alzheimer's disease-related mutations, a loss of neuronal membrane potassium-chloride cotransporter KCC2, responsible for maintaining the robustness of GABAA-mediated inhibition, occurs pre-symptomatically in the hippocampus and prefrontal cortex. KCC2 downregulation was inversely correlated with the age-dependent increase in amyloid-β 42 (Aβ42). Acute administration of Aβ42 caused a downregulation of membrane KCC2. Loss of KCC2 resulted in impaired chloride homeostasis. Preventing the decrease in KCC2 using long term treatment with CLP2"],"journal":["Brain : a journal of neurology"],"pubmed_title":["Restoring neuronal chloride extrusion reverses cognitive decline linked to Alzheimer's disease mutations."],"pmcid":["PMC10690023"],"funding_grant_id":["269555","159906","156040","06507","TR192089","390930"],"pubmed_authors":["Godin AG","Inayat S","Sansonetti R","Rezaei E","Wang F","Isabel D","Nazari M","De Koninck Y","McAllister BB","Dudley JC","Paquet ME","Bourbonnais J","Degagne P","Mohajerani MH","Hamel JP","Froux L","Keramidis I","Barbeau A"],"additional_accession":[]},"is_claimable":false,"name":"Restoring neuronal chloride extrusion reverses cognitive decline linked to Alzheimer's disease mutations.","description":"Disinhibition during early stages of Alzheimer's disease is postulated to cause network dysfunction and hyperexcitability leading to cognitive deficits. However, the underlying molecular mechanism remains unknown. Here we show that, in mouse lines carrying Alzheimer's disease-related mutations, a loss of neuronal membrane potassium-chloride cotransporter KCC2, responsible for maintaining the robustness of GABAA-mediated inhibition, occurs pre-symptomatically in the hippocampus and prefrontal cortex. KCC2 downregulation was inversely correlated with the age-dependent increase in amyloid-β 42 (Aβ42). Acute administration of Aβ42 caused a downregulation of membrane KCC2. Loss of KCC2 resulted in impaired chloride homeostasis. Preventing the decrease in KCC2 using long term treatment with CLP2","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Dec","modification":"2026-06-03T19:57:17.738Z","creation":"2025-05-18T10:39:22.714Z"},"accession":"S-EPMC10690023","cross_references":{"pubmed":["37551444"],"doi":["10.1093/brain/awad250"]}}