Selective activation of ABCA1/ApoA1 signaling in the V1 by magnetoelectric stimulation ameliorates depression via regulation of synaptic plasticity

Qingbo Lu; Fangfang Wu; Jiao Jiao; Le Xue; Ruize Song; Yachen Shi; Yan Kong; Jianfei Sun; Ning Gu; Ming-Hu Han; Zhijun Zhang

doi:10.1016/j.isci.2022.104201

Selective activation of ABCA1/ApoA1 signaling in the V1 by magnetoelectric stimulation ameliorates depression via regulation of synaptic plasticity

iScience. 2022 Apr 4;25(5):104201. doi: 10.1016/j.isci.2022.104201. eCollection 2022 May 20.

Authors

Qingbo Lu¹, Fangfang Wu², Jiao Jiao¹, Le Xue³, Ruize Song¹, Yachen Shi¹, Yan Kong⁴, Jianfei Sun³, Ning Gu³, Ming-Hu Han^{5

6}, Zhijun Zhang^{1

6

7}

Affiliations

¹ Department of Neurology, Affiliated Zhongda Hospital, School of Medicine, Institution of Neuropsychiatry, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, Jiangsu 210096, China.
² Department of Pharmacology, Nanjing University of Chinese Medicine, Nanjing, 210046, China.
³ State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210009, China.
⁴ Department of Biochemistry and Molecular Biology, School of Medicine, Southeast University, Nanjing, 210009, China.
⁵ Department of Pharmacological Sciences, Department of Neuroscience, Center for Affective Neuroscience, and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁶ Department of Mental Health and Public Health, Faculty of Life and Health Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
⁷ Research Center for Brain Health, Pazhou Lab, Guangzhou, Guangdong 510330, China.

Abstract

Emerging evidence suggests that dysfunction of the visual cortex may be involved in major depressive disorder (MDD). However, the underlying mechanisms remain unclear. We previously established that combined magnetic stimulation system treatment (c-MSST) resulted in an antidepressant effect in mice. In the present study, we found that V1-targeted c-MSST induced significant antidepressant effects in chronic unpredictable mild stress (CUMS)- and lipopolysaccharide (LPS)-treated mice. Proteomic screening investigation and repeatable validation revealed that expression of the V1 neuronal ATP-binding cassette transporter A1 (ABCA1) and apolipoprotein A-1 (ApoA1) was downregulated in CUMS mice, an effect that was normalized by c-MSST. Neuron-specific knockdown of ABCA1 in V1 blocked c-MSST's antidepressant effects. Mechanistically, CUMS reduced dendritic spine density and long-term plasticity in V1, and these deficits were reversed by c-MSST. V1-targeted c-MSST was found to induce rapid antidepressant effects that are mediated by alterations in synaptic plasticity via the ABCA1/ApoA1 signaling pathway in V1.

Keywords: Cellular neuroscience; Molecular neuroscience; Techniques in neuroscience.