%0 Journal Article %T Crucial role of FABP3 in $\alpha$syn-induced reduction of septal GABAergic neurons and cognitive decline in mice %+ Tohoku University [Sendai] %+ Centre National de la Recherche Scientifique (CNRS) %+ Molecular Imaging Research Center [Fontenay-aux-Roses] (MIRCen) %+ Service MIRCEN (MIRCEN) %A Matsuo, Kazuya %A Yabuki, Yasushi %A Melki, Ronald %A Bousset, Luc %A Owada, Yuji %A Fukunaga, Kohji %< avec comité de lecture %@ 1661-6596 %J International Journal of Molecular Sciences %I MDPI %V 22 %P 400 %8 2021-01-01 %D 2021 %R 10.3390/ijms22010400 %K alpha-synuclein %K cognition %K fatty acid-binding protein %K gamma-aminobutyric acid %K medial septum %Z Life Sciences [q-bio]Journal articles %X In synucleinopathies, while motor symptoms are thought to be attributed to the accumulationof misfolded a-synuclein (aSyn) in nigral dopaminergic neurons, it remains to be elucidatedhow cognitive decline arises. Here, we investigated the effects of distinct aSyn strains on cognitionand the related neuropathology in the medial septum/diagonal band (MS/DB), a key region forcognitive processing. Bilateral injection of aSyn fibrils into the dorsal striatum potently impairedcognition in mice. The cognitive decline was accompanied by accumulation of phosphorylated aSynat Ser129 and reduction of gamma-aminobutyric acid (GABA)-ergic but not cholinergic neurons inthe MS/DB. Since we have demonstrated that fatty acid-binding protein 3 (FABP3) is critical for aSynneurotoxicity in nigral dopaminergic neurons, we investigated whether FABP3 also participates inaSyn pathology in the MS/DB and cognitive decline. FABP3 was highly expressed in GABAergic butrarely in cholinergic neurons in the MS/DB. Notably, Fabp3 deletion antagonized the accumulationof phosphorylated aSyn, decrease in GABAergic neurons, and cognitive impairment caused byaSyn fibrils. Overall, the present study indicates that FABP3 mediates aSyn neurotoxicity in septalGABAergic neurons and the resultant cognitive impairment, and that FABP3 in this subpopulationcould be a therapeutic target for dementia in synucleinopathies. %G English %2 https://cea.hal.science/cea-03116076/document %2 https://cea.hal.science/cea-03116076/file/ijms-22-00400-v2.pdf %L cea-03116076 %U https://cea.hal.science/cea-03116076 %~ CEA %~ CNRS %~ CEA-UPSAY %~ UNIV-PARIS-SACLAY %~ JACOB %~ CEA-DRF %~ MIRCEN %~ TEST-HALCNRS %~ UNIVERSITE-PARIS-SACLAY