Decreased hippocampal neurogenesis is involved in cognitive dysfunction induced by thiamine deficiency / 中华神经科杂志

ABSTRACT

Objective To investigate the influence of thiamine deficiency(TD)at early pre- pathological lesion stage on cognitive function and the correlation between cognitive dysfunction and hippocampal neurogenesis.Methods TD mouse model was prepared by feeding a thiamine-depleted diet. Learning and memory functions of TD mice were tested with Y-maze.Hippoeampal neurogenesis was studied with bromodeoxyuridine(BrdU),proliferative cell nuclear antigen(PCNA),and Doublecortin(Dcx) immunohistochemical staining on the 7th(TD7),9th,14th and TD25th day.Results TD9 mice without pathological impairment and cholinergic nerve degeneration needed more times of training(22.3?2.2)in the learning test of Y maze compared with the controls(13.5?3.5).Correspondingly,the numbers of BrdU-positive ceils and the immunoreactivity of Dcx decreased significantly in the TD9 mice(19.8?0.4, 1537.2?50.2 vs 23.9?0.3,2688.9?127.9 pixels/mm~2).Thiamine re-administration reversed the declined hippocampal neurogenesisthe number of BrdU-positive cells was 23.6?1.9 and Dcx immunoreactivity was 2052.3?269.6 pixels/mm~2the impaired learning ability was simultaneously restored,with the number of total training trial being 16.8?0.5.Conclusion The decreased hippocampal neurogenesis contributes to retarded learning ability at early pre-pathological lesion stage of TD.