Thiamine deficiency contributes to synapse and neural circuit defects

Biol Res. 2018 Sep 19;51(1):35. doi: 10.1186/s40659-018-0184-5.

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, Aβ 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.

Keywords: Alzheimer’s disease; Amyloid-β; Synaptic dysfunction; Thiamine deficiency.

MeSH terms

  • Alzheimer Disease / etiology*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Blotting, Western
  • Dendritic Spines / metabolism
  • Diphosphotransferases / metabolism
  • Glucose / metabolism
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Male
  • Mice, Inbred C57BL
  • Neurons / physiology*
  • Random Allocation
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Synapses / physiology*
  • Synaptic Transmission / physiology
  • Thiamine Deficiency / complications*
  • Thiamine Deficiency / metabolism*
  • Thiamine Deficiency / physiopathology
  • Thiamine Pyrophosphate / deficiency*
  • Thiamine Pyrophosphate / metabolism

Substances

  • Amyloid beta-Peptides
  • Diphosphotransferases
  • Glucose
  • Thiamine Pyrophosphate