Repetitive Transcranial Magnetic Stimulation-Mediated Neuroprotection in the 5xFAD Mouse Model of Alzheimer's Disease Through GABRG2 and SNAP25 Modulation.

Autor: Wang J; Department of Neurology, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China., Zhou C; Core Facilities and Centers, Hebei Medical University, Shijiazhuang, 050017, China., Huang Z; Department of Stomatology, People's Hospital, Shizhu Tujia Autonomous County, Chongqing, 409100, China., Ji X; Laboratory of Neurobiology, Hebei Medical University, Zhongshan Donglu No.361, ShijiazhuangHebei Province, 050017, China.; Neuroscience Research Center, Hebei Medical University, Shijiazhuang, 050017, China., Cui R; Neuroscience Research Center, Hebei Medical University, Shijiazhuang, 050017, China., Kang Y; Laboratory of Neurobiology, Hebei Medical University, Zhongshan Donglu No.361, ShijiazhuangHebei Province, 050017, China.; Neuroscience Research Center, Hebei Medical University, Shijiazhuang, 050017, China., Zhang G; Neuroscience Research Center, Hebei Medical University, Shijiazhuang, 050017, China., Wang Y; Laboratory of Neurobiology, Hebei Medical University, Zhongshan Donglu No.361, ShijiazhuangHebei Province, 050017, China., Zhang T; Laboratory of Neurobiology, Hebei Medical University, Zhongshan Donglu No.361, ShijiazhuangHebei Province, 050017, China. zhangtianyun@hebmu.edu.cn.
Jazyk: angličtina
Zdroj: Molecular neurobiology [Mol Neurobiol] 2024 Jul 25. Date of Electronic Publication: 2024 Jul 25.
DOI: 10.1007/s12035-024-04354-7
Abstrakt: Alzheimer's disease (AD) is a leading neurodegenerative disorder with substantial impacts on cognition and behavior. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, has been used to treat various neuropsychiatric disorders, but its efficacy in AD has not been thoroughly investigated. This study examines the neuroprotective effects of rTMS in the 5xFAD mouse model of AD, with a particular focus on its modulation of GABAergic neuronal activity via the GABRG2 and SNAP25 proteins. Transcriptomic sequencing of rTMS-treated 5xFAD mice revealed 32 genes influenced by the treatment, among which GABRG2 was identified as a critical modulatory target. Electrophysiological assessments, including whole-cell patch clamp recordings from frontal cortex neurons, demonstrated significant alterations in inhibitory synaptic currents following rTMS. Subsequent experiments involved sh-GABRG2 transduction combined with rTMS treatment (20Hz, 14 days), examining behavioral responses, GABAergic neuron functionality, cortical GABA expression, cerebrospinal fluid GABA concentrations, β-amyloid accumulation, and pro-inflammatory cytokine levels. The results indicated notable improvements in behavioral performance, enhanced functionality of GABAergic neurons, and reductions in β-amyloid deposition and neuroinflammation after rTMS treatment. Further analysis revealed that SNAP25 overexpression could counteract the negative effects of GABRG2 silencing, highlighting the crucial role of SNAP25 downstream of GABRG2 in mediating rTMS's therapeutic effects in AD. This research highlights rTMS's potential to modulate synaptic and vesicular transport mechanisms, offering a promising avenue for ameliorating symptoms of AD through neuroprotective pathways.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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