title: Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke-Korsakoff syndrome.
abstract: Patients with severe Wernicke-Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation.
authors: a Faculty of Applied Bioscience, Department of Bioscience , Tokyo University of Agriculture , Tokyo , Japan.
authors: Hiroyoshi
authors: H
authors: Inaba
authors: a Faculty of Applied Bioscience, Department of Bioscience , Tokyo University of Agriculture , Tokyo , Japan.
authors: Takuya
authors: T
authors: Kishimoto
authors: a Faculty of Applied Bioscience, Department of Bioscience , Tokyo University of Agriculture , Tokyo , Japan.
authors: Satoru
authors: S
authors: Oishi
authors: a Faculty of Applied Bioscience, Department of Bioscience , Tokyo University of Agriculture , Tokyo , Japan.
authors: Kan
authors: K
authors: Nagata
authors: a Faculty of Applied Bioscience, Department of Bioscience , Tokyo University of Agriculture , Tokyo , Japan.|b Core Research for Evolutional Science and Technology , Japan Science and Technology Agency , Saitama , Japan.
authors: Shunsuke
authors: S
authors: Hasegawa
authors: a Faculty of Applied Bioscience, Department of Bioscience , Tokyo University of Agriculture , Tokyo , Japan.
authors: Tamae
authors: T
authors: Watanabe
authors: a Faculty of Applied Bioscience, Department of Bioscience , Tokyo University of Agriculture , Tokyo , Japan.|b Core Research for Evolutional Science and Technology , Japan Science and Technology Agency , Saitama , Japan.
authors: Satoshi
authors: S
authors: Kida
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000503:physiopathology; D000818:Animals; D001259:Ataxia / Q000150:complications; D001835:Body Weight; D049229:Dendritic Spines / Q000473:pathology*; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D020915:Korsakoff Syndrome; D008568:Memory; D051379:Mice; D010641:Phenotype; D011745:Pyrithiamine / Q000494:pharmacology; D013832:Thiamine Deficiency / Q000139:chemically induced / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D011745:Pyrithiamine
keywords: Wernicke–Korsakoff syndrome; hippocampus-dependent memory; microendophenotypes; thiamine deficiency; vitamin B1