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Thiamine Deficiency Induces Endoplasmic Reticulum Stress in Neurons
Journal article   Peer reviewed

Thiamine Deficiency Induces Endoplasmic Reticulum Stress in Neurons

Xin Wang, Bingwei Wang, Zhiqin Fan, Xianglin Shi, Zun-Ji Ke and Jia Luo
Neuroscience, Vol.144(3), pp.1045-1056
02/09/2007
DOI: 10.1016/j.neuroscience.2006.10.008
PMCID: PMC1819404
PMID: 17137721
url
https://www.ncbi.nlm.nih.gov/pmc/articles/1819404View
Open Access

Abstract

Thiamine (vitamin B1) deficiency (TD) causes region selective neuronal loss in the brain; it has been used to model neurodegeneration that accompanies mild impairment of oxidative metabolism. The mechanisms for TD-induced neurodegeneration remain incompletely elucidated. Inhibition of protein glycosylation, perturbation of calcium homeostasis and reduction of disulfide bonds provoke the accumulation of unfolded proteins in the endoplasmic reticulum (ER), and cause ER stress. Recently, ER stress has been implicated in a number of neurodegenerative models. We demonstrated here that TD up-regulated several markers of ER stress, such as GRP78, GADD153/Chop, phosphorylation of eIF2α and cleavage of caspase-12 in the cerebellum and the thalamus of mice. Furthermore, ultrastructural analysis by electron microscopic study revealed an abnormality in ER structure. To establish an in vitro model of TD in neurons, we treated cultured cerebellar granule neurons (CGNs) with amprolium, a potent inhibitor of thiamine transport. Exposure to amprolium caused apoptosis and the generation of reactive oxygen species in CGNs. Similar to the observation in vivo , TD up-regulated markers for ER stress. Treatment of a selective inhibitor of caspase-12 significantly alleviated amprolium-induced death of CGNs. Thus, ER stress may play a role in TD-induced brain damage.
 cell death cerebellum neurodegeneration nutrition vitamin B1

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