ABSTRACT
BACKGROUND: The previous studies have demonstrated the reduction of thiamine diphosphate is specific to Alzheimer's disease (AD) and causal factor of brain glucose hypometabolism, which is considered as a neurodegenerative index of AD and closely correlates with the degree of cognitive impairment. The reduction of thiamine diphosphate may contribute to the dysfunction of synapses and neural circuits, finally leading to cognitive decline. RESULTS: To demonstrate this hypothesis, we established abnormalities in the glucose metabolism utilizing thiamine deficiency in vitro and in vivo, and we found dramatically reduced dendrite spine density. We further detected lowered excitatory neurotransmission and impaired hippocampal long-term potentiation, which are induced by TPK RNAi in vitro. Importantly, via treatment with benfotiamine, Aß induced spines density decrease was considerably ameliorated. CONCLUSIONS: These results revealed that thiamine deficiency contributed to synaptic dysfunction which strongly related to AD pathogenesis. Our results provide new insights into pathogenesis of synaptic and neuronal dysfunction in AD.
Subject(s)
Animals , Male , Synapses/physiology , Thiamine Deficiency/complications , Thiamine Deficiency/metabolism , Thiamine Pyrophosphate/deficiency , Alzheimer Disease/etiology , Alzheimer Disease/metabolism , Neurons/physiology , Thiamine Deficiency/physiopathology , Thiamine Pyrophosphate/metabolism , Random Allocation , Blotting, Western , Amyloid beta-Peptides/metabolism , Rats, Sprague-Dawley , Diphosphotransferases/metabolism , Synaptic Transmission/physiology , Dendritic Spines/metabolism , Alzheimer Disease/physiopathology , Real-Time Polymerase Chain Reaction , Glucose/metabolism , Hippocampus/physiopathology , Hippocampus/metabolism , Mice, Inbred C57BLABSTRACT
Os objetivos do presente trabalho foram estdar os efeitos da deficiência aguda de tiamina no crescimento e na resposta quimiterápica de um fibro-histiocitoma maligno no rato. Para tanto, ratos foram inoculados por via subcutânea com suspensäo de células tumorais e divididos em quadro grupos, de 10 animais cada: DCT - alimentados com dieta sem tiamina; TGT - alimentados com dieta controle; e TVC - alimentados com dieta controle e tratados com SVC. Os animais tratados com SVC (DVC e TVC) apresentaram diminuiçäo de volume tumoral quando comparados com os näo tratados (DCT e TCT). Entretanto, näo houve alteraçäo no volume tumoral de animais carentes em tiamina tratados (DVC) em relaçäo àqueles tratados e com dieta controle (DCT). Estes dados indicam que a deficiência aguda de tiamina per se näo altera o cresciento do FHM como também näo modifica a resposta de tumor frente à quimioterapia com SVC.