Electroconvulsive Seizure Normalizes Motor Deficits and Induces Autophagy Signaling in the MPTP-Induced Parkinson Disease Mouse Model

• 영문명: Electroconvulsive Seizure Normalizes Motor Deficits and Induces Autophagy Signaling in the MPTP-Induced Parkinson Disease Mouse Model
• 발행기관: 대한신경정신의학회
• 저자명: Seonghoo Huh Hyun Sook Yu Nuree Kang Yong Min Ahn Yong Sik Kim Se Hyun Kim
• 간행물 정보: 『Psychiatry Investigation』제20권 제3호, 273~283쪽, 전체 11쪽
• 주제분류: 의약학 > 정신과학
• 파일형태: PDF
• 발행일자: 2023.03.31

영문 초록

Objective Electroconvulsive seizure (ECS) is a potent treatment modality for various neuropsychiatric diseases, including Parkinson disease (PD). Recent animal studies showed that repeated ECS activates autophagy signaling, the impairment of which is known to be involved in PD. However, the effectiveness of ECS on PD and its therapeutic mechanisms have not yet been investigated in detail. Methods Systemic injection of a neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), which destroys dopaminergic neurons in the substantia nigra compacta (SNc), in mice was utilized to induce an animal model of PD. Mice were treated with ECS 3 times per week for 2 weeks. Behavioral changes were measured with a rotarod test. Molecular changes related to autophagy signaling in midbrain including SNc, striatum, and prefrontal cortex were analyzed with immunohistochemistry and immunoblot analyses. Results Repeated ECS treatments normalized the motor deficits and the loss of dopamiergic neurons in SNc of the MPTP PD mouse model. In the mouse model, LC3-II, an autophagy marker, was increased in midbrain while decreased in prefrontal cortex, both of which were reversed by repeated ECS treatments. In the prefrontal cortex, ECS-induced LC3-II increase was accompanied with AMP-activated protein kinase (AMPK)-Unc-51-like kinase 1-Beclin1 pathway activation and inhibition of mamalian target of rapamycin signaling which promotes autophagy initiation. Conclusion The findings revealed the therapeutic effects of repeated ECS treatments on PD, which could be attributed to the neuroprotective effect of ECS mediated by AMPK-autophagy signaling.

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키워드

AMP-activated protein kinase Autophagy Electroconvulsive therapy Mammalian target of rapamycin Parkinson disease