Thiamine deficiency contributes to synapse and neural circuit defects

Abstract

BackgroundThe 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.ResultsTo 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, Aβ induced spines density decrease was considerably ameliorated.ConclusionsThese 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.

Metabolic Dysregulation Contributes to the Progression of Alzheimer’s Disease

“…Furthermore, the activities of transketolase and their common coenzymes thiamine diphosphate, GSH peroxidase, glutathione-S-transferase, and δ-aminolevulinate dehydratase (δ-ALA-D) have all been demonstrated to be decreased in AD (Sheu et al, 1988;Mastrogiacomo et al, 1996;Ansari and Scheff, 2010;Yu et al, 2018). Multiple metabolites altered by ApoE are identified within the PPP, including gluconolactone, gluconate, and G6P (Johnson et al, 2017).…”

Thiamine deficiency affects glucose transport and β‐oxidation in rats

“…Thiamine deficiency (TD) causes besides the weight loss, also disorders of nervous system and cardiomyopathy (Hoffman., ; Krasicka, Gralak, Sieranska, & Kulasek, ). It may decrease the membrane conductance, cause disorders in ATP production (Oliveira, Galan, Ribeiro, & Santos Cruz, ), brain failures (Aikawa et al, ; Ke, DeGiorgio, Volpe, & Gibson, ; Yu et al, ) and liver disorders (Hernandez‐Vazquez et al, ). Moreover, the TD may result in an increase of the frequency of death of cardiac cells (Zangen & Shainberg, ).…”

Gene variations in Autism Spectrum Disorder are associated with alternation of gut microbiota, metabolites and cytokines

“…The thiamine deficiency was observed in Alzheimer’s disease and contribute to synapse and neural circuit defects. 45 …”

“…The thiamine deficiency was observed in Alzheimer's disease and contribute to synapse and neural circuit defects. 45 Previous studies have demonstrated that ASD genetic risk can act in part through expression quantitative trait loci, 46 namely, eQTL, and epigenetic regulation, 47 such as meQTL. Accordingly, we explored the association between microbes and the eQTL or meQTL SNVs.…”