Impaired hippocampal neurogenesis is involved in cognitive dysfunction induced by thiamine deficiency at early pre-pathological lesion stage.
It has not been reported whether thiamine deficiency (TD) affects hippocampal neurogenesis or not. Here, we explored the influence of TD at early pre-pathological lesion stage on hippocampal neurogenesis and the correlation between affected hippocampal neurogenesis and cognitive dysfunction. We prepared TD mouse model by feeding a thiamine-depleted diet. Learning and memory functions of TD mice were tested with Y-maze. Hippocampal neurogenesis was studied with BrdU, PCNA, Dcx, and NeuN immunohistochemical staining. The results showed significant decline in learning ability and hippocampal neurogenesis simultaneously since 9-days of treatment when the model mice did not exhibit regular pathological lesion, the loss of cholinergic neurons, decrease of NeuN-positive hippocampal cell, and abnormal long-term potentiation of hippocampal CA1 and CA3. Re-administering thiamine reversed the weakened learning ability as well as the impaired hippocampal neurogenesis induced by TD at early pre-pathological lesion stage. The present study demonstrated that hippocampal neurogenesis was vulnerable to TD and the impaired hippocampal neurogenesis is greatly involved in cognitive dysfunction induced by TD at early pre-pathological lesion stage.
Zhao
Na
N
Department of Neurology, Zhongshan Hospital, Fudan University, China.
Zhong
Chunjiu
C
Wang
Yang
Y
Zhao
Yanling
Y
Gong
Neng
N
Zhou
Guomin
G
Xu
Tianle
T
Hong
Zhen
Z
D000818:Animals; D001522:Behavior, Animal; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology*; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D000089662:Doublecortin Protein; D004558:Electric Stimulation; D005526:Food, Formulated / Q000009:adverse effects; D006624:Hippocampus / Q000473:pathology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology / Q000528:radiation effects; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D013832:Thiamine Deficiency / Q000150:complications* / Q000209:etiology; D013997:Time Factors
C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D009419:Nerve Tissue Proteins; D002795:Choline O-Acetyltransferase; D001973:Bromodeoxyuridine