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
En nuestro pais, Guatemala, nunca se habia investigado lo que es la encefalopatia de Wernicke que traducido se refiere a la deficiencia de la Tiamina (Vitamina B1)/. Para poder realizar nuestra investigación tomamos una muestra de 30 pacientes, adultos de uno y otro sexo, excluyéndose los pacientes que presentaban alteraciones del estado de conciencia con diagnóstico de hipertensión arterial, accidente cerebro vascular, alcohólicos, abcesos cerebrales, (alcohólicos) o traumatismo cerebral. Que ingresaron por bez primera al hospital sin diagnóstico; al llegar el paciente a la emergencia, inmediatametne se procedió extraer 5 cc de sangre, la que se centrifugaba, se extraia el suero. El cual se hacia reaccionar posteriormente con 4 reactivos (blanco muestra Standar y control) específico para medir el incremento en sangre de la enzima Tiamina pirofosfato (ver metododologia)