1. 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
- Author
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Satoshi Kida, Shunsuke Hasegawa, Tamae Watanabe, Hiroyoshi Inaba, Kan Nagata, Takuya Kishimoto, and Satoru Oishi
- Subjects
0301 basic medicine ,vitamin B1 ,medicine.medical_specialty ,Dendritic spine ,Dendritic Spines ,hippocampus-dependent memory ,microendophenotypes ,Hippocampus ,Hippocampal formation ,Applied Microbiology and Biotechnology ,Biochemistry ,Article ,Analytical Chemistry ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Memory ,Internal medicine ,medicine ,Regular Paper ,Memory impairment ,Animals ,Molecular Biology ,Wernicke–Korsakoff syndrome ,thiamine deficiency ,business.industry ,Dentate gyrus ,Organic Chemistry ,Body Weight ,General Medicine ,medicine.disease ,Amygdala ,030104 developmental biology ,Endocrinology ,Korsakoff Syndrome ,Phenotype ,nervous system ,Pyrithiamine ,Endophenotype ,Thiamine ,Ataxia ,business ,030217 neurology & neurosurgery ,Biotechnology - 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., Graphical abstract PTD mice showed deficits in hippocampus-dependent memory and loss of neurons and spines in the hippocampus.
- Published
- 2016