Journal article
Autophagy Alleviates Neurodegeneration Caused by Mild Impairment of Oxidative Metabolism
Journal of neurochemistry, Vol.126(6), pp.805-818
09/2013
DOI: 10.1111/jnc.12268
PMCID: PMC3759557
PMID: 23586593
Abstract
Thiamine deficiency (TD) causes mild impairment of oxidative metabolism and region-selective neuronal loss in the brain, which may be mediated by neuronal oxidative stress, endoplasmic reticulum stress, and neuroinflammation. TD-induced brain damage is used to model neurodegenerative disorders, and the mechanism for the neuronal death is still unclear. We hypothesized that autophagy might be activated in the TD brain and play a protective role in TD induced neuronal death. Our results demonstrated that TD induced the accumulation of autophagosomes in neurons of the thalamus measured by transmission electron microscopy, and the upregulation of autophagic markers: LC3-II, Atg5 and Beclin1 as measured with western blotting. TD also increased the expression of autophagic markers and induced LC3 puncta in SH-SY5Y neuroblastoma cells. TD-induced expression of autophagic markers was reversed once thiamine was re-administered. Both inhibition of autophagy by wortmannin and Beclin1 siRNA potentiated TD-induced death of SH-SY5Y cells. In contrast, activation of autophagy by rapamycin alleviated cell death induced by TD. Intraperitoneal injection of rapamycin stimulated neuronal autophagy and attenuated TD-induced neuronal death and microglia activation in the submedial thalamus nucleus (SmTN). TD inhibited the phosphorylation of p70S6 kinase, suggesting mTOR/p70S6 kinase pathway was involved the TD-induced autophagy. These results suggest that autophagy is neuroprotective in response to TD-induced neuronal death in the central nervous system. This opens a potential therapeutic avenue for neurodegenerative diseases caused by mild impairment of oxidative metabolism.
Details
- Title: Subtitle
- Autophagy Alleviates Neurodegeneration Caused by Mild Impairment of Oxidative Metabolism
- Creators
- Ya Meng - Chinese Academy of SciencesYue Yong - Chinese Academy of SciencesGuang Yang - Chinese Academy of SciencesHanqing Ding - Chinese Academy of SciencesZhiqin Fan - Chinese Academy of SciencesYifen Tang - Chinese Academy of SciencesJia Luo - University of KentuckyZun-Ji Ke - Shanghai Institutes for Biological Sciences
- Resource Type
- Journal article
- Publication Details
- Journal of neurochemistry, Vol.126(6), pp.805-818
- DOI
- 10.1111/jnc.12268
- PMID
- 23586593
- PMCID
- PMC3759557
- NLM abbreviation
- J Neurochem
- ISSN
- 0022-3042
- eISSN
- 1471-4159
- Grant note
- R21 AA019693 || AA / National Institute on Alcohol Abuse and Alcoholism : NIAAA R01 AA015407 || AA / National Institute on Alcohol Abuse and Alcoholism : NIAAA
- Language
- English
- Date published
- 09/2013
- Academic Unit
- Pathology
- Record Identifier
- 9984201118302771
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