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6088670 
Journal Article 
The neuroprotective effect of deep brain stimulation at nucleus basalis of Meynert in transgenic mice with Alzheimer's disease 
Huang, C; Chu, H; Ma, Y; Zhou, Z; Dai, C; Huang, X; Fang, L; Ao, Q; Huang, D 
2019 
Yes 
Brain Stimulation
ISSN: 1935-861X 
12 
1 
161-174 
English 
30181106 
WOS:000453259000020 
BACKGROUND: Alzheimer's disease (AD) is the most common type of dementia and mainly treated by drugs, while the therapeutic outcomes are very limited. This study aimed to determine the optimized parameters of deep brain stimulation (DBS) which was applied to the treatment of AD and propose the involved mechanisms.

METHODS: Amyloid-β precursor protein/Presenilin1 (APP/PS1) transgenic mice were used and received DBS at nucleus basalis of Meynert (NBM). The optimized parameters of DBS were determined by using different stimulation frequencies, durations and ages of mice under Morris water maze test. The involved mechanisms and the possible signal pathways were also investigated.

RESULTS: The optimized parameters for DBS were high frequency (100 Hz) for 21 days starting from early age (4 months old). Under the above parameters, the soluble Aβ40 and Aβ42 in the hippocampus and cortex were down-regulated significantly. DBS increased survival neurons and reduced apoptotic cells in the hippocampus and cortex. Meanwhile, the apoptosis-related proteins caspase-3, caspase-8 and Bid were down-regulated. Moreover, DBS caused a significant increase of superoxide dismutase, glutathione peroxidase and choline acetyltransferase activity as well as a decrease of methane dicarboxylic aldehyde content and acetylcholine esterase activity. Phosphorylation of Akt (p-Akt)/total Akt (t-Akt) was up-regulated while p-extracellular signal-regulated kinase 1/2 (ERK1/2)/t-ERK1/2 was down-regulated. The neuroprotective effect of DBS was attenuated by their inhibitors.

CONCLUSIONS: NBM-DBS starting from 4 months of age for 21 days at a high frequency (100 Hz) has therapeutic effects on AD through activating phosphatidylinositol 3'-kinase (PI3K)/Akt pathway and inhibiting ERK1/2 pathway. 
Alzheimer's disease; Deep brain stimulation; Nucleus basalis of Meynert; APP/PS1 transgenic mice; Morris water maze