Decreased hippocampal neurogenesis is involved in cognitive dysfunction induced by thiamine deficiency

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. Hippocampal 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 cells 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 neurogenesis: the number of BrdU-positive cells was 23.6 ± 1.9 and Dcx immunoreactivity was 2052.3 ± 269.6 pixels/mm ²: the 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.