期刊
AGING-US
卷 12, 期 7, 页码 6324-6339出版社
IMPACT JOURNALS LLC
DOI: 10.18632/aging.103026
关键词
epilepsy; deep brain stimulation; anterior thalamic nuclei; autophagy; brain-derived neurotrophic factor
资金
- National Nature Science Foundation of China [81701268, 61761166004, 81830033]
- Beijing Municipal Administration of Hospitals' Ascent Plan [DFL20150503]
- capital health research and development of special [2018-2Z1076]
- China Postdoctoral Science Foundation [2018T110120]
Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is effective in treating temporal lobe epilepsy (TLE) and protects hippocampal neurons. Autophagy plays an essential role in epileptogenesis; however, the underlying effect of autophagy on ANT-DBS-mediated neuroprotection remains unclear. A monkey model of epilepsy was established by injecting kainic acid into the hippocampus and amygdala using a robot-assisted system. ANT-DBS was delivered in the chronic stage of the epileptic model and continued for 8 weeks. We found that ANT-DBS reduced the frequency of seizures and exerted neuroprotective effects via activating autophagy in hippocampal neurons. ANT-DBS increased light chain 3 (LC3) II level and co-localization of LC3 and lysosomal-associated membrane protein-1, accompanied by decreased expression of the autophagy substrate ubiquitin-binding protein p62, suggesting increased autophagosome formation. Most importantly, brain-derived neurotrophic factor (BDNF) -tropomyosin-related kinase type B (TrkB) pathway were involved in the regulation of autophagy. Both protein levels were reduced by ANT-DBS, and there was less phosphorylation of downstream regulators, extracellular signal-regulated kinase and Akt, followed by inactivation of mammalian target of rapamycin complex 1. Taken together, chronic ANT-DBS exerts neuroprotective effects on hippocampal neurons through inducing autophagy via suppressing the BDNF-TrkB pathway in a TLE monkey model.
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