The neuroprotective effect of deep brain stimulation at nucleus basalis of Meynert in transgenic mice with Alzheimer's disease
Authors: Dongya Huang
Chuanfu Dai
Yu Ma
Xiaowen Huang
Chuyi Huang
Heling Chu
Qiang Ao
Liang Fang
Zaiying Zhou
Journal: Brain Stimulation (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: APP/PS1 transgenic mice; Alzheimer's disease; Deep brain stimulation; Morris water maze; Nucleus basalis of Meynert.
Affiliations: Department of Neurology, Shanghai East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Shanghai 200120, China., Department of Neurology, Huashan Hospital, Fudan University, No.12 Mid. Wulumuqi Road, Shanghai 200040, China., Department of Neurosurgery, Tsinghua University Yuquan Hospital, No. 5 Shijingshan Road, Shijingshan District, Beijing 100049, China., Center for Statistical Science of Tsinghua University, Beijing 100084, China., Department of Otolaryngology, Head and Neck Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China., Department of Orthopedics, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China., Department of Mathematical Sciences, Tsinghua University, Beijing 100084, China., Department of Tissue Engineering, China Medical University, No. 77 Puhe Road, Shenyang Liaoning, 110122, China. Electronic address: ., Department of Neurology, Shanghai East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Shanghai 200120, China. Electronic address: .

Abstract:  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-Œ≤ 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 AŒ≤40 and AŒ≤42 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. 

Retracted: No

PubPeer comments:
 The reference in the following selection in the discussion section of this paper is misleading.  *All patients in this study were taking typical and or atypical types of antipsychotic medication. This medication confound has been present in all prior 40-Hz ASSR SZ studies, and in one study, patients taking atypical antipsychotics (clozapine, olanzapine, and risperidone) had greater 40-Hz power than HC subjects (45).* The cited paper, which is as following is one of the many review articles cited in this paper. But here the cited paper has no mention of any of the above-mentioned studies.  *45. Rotaru DC, Lewis DA, Gonzalez-Burgos G (2012): The role of glutamatergic inputs onto parvalbumin-positive interneurons: Relevance for schizophrenia. Rev Neurosci 23:97u2013109* If the author would have been more diligent in citing the primary sources it would have been much easier to access the original claims. ,