首页|Botulinum neurotoxin A ameliorates depressive-like behavior in a reserpine-induced Parkinson's disease mouse model via suppressing hippocampal microglial engulfment and neuroinflammation

Botulinum neurotoxin A ameliorates depressive-like behavior in a reserpine-induced Parkinson's disease mouse model via suppressing hippocampal microglial engulfment and neuroinflammation

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Depression is one of the common non-motor symptoms of Parkinson's disease(PD).In the clinic,botulinum neurotoxin A(BoNT/A)has been used to treat depression.In this study,we investigated the mechanisms underlying the anti-depressive effect of BoNT/A in a PD mouse model.Mice were administered reserpine(3 μg/mL in the drinking water)for 10 weeks.From the 10th week,BoNT/A(10 U.kg-1·d-1)was injected into the cheek for 3 consecutive days.We showed that chronic administration of reserpine produced the behavioral phenotypes of depression and neurochemical changes in the substantia nigra pars compacta(SNpc)and striatum.BoNT/A treatment significantly ameliorated the depressive-like behaviors,but did not improve TH activity in SNpc of reserpine-treated mice.We demonstrated that BoNT/A treatment reversed reserpine-induced complement and microglia activation in the hippocampal CA1 region.Furthermore,BoNT/A treatment significantly attenuated the microglial engulfment of presynaptic synapses,thus ameliorating the apparent synapse and spine loss in the hippocampus in the reserpine-treated mice.Moreover,BoNT/A treatment suppressed microglia-mediated expression of pro-inflammatory cytokines TNF-α and IL-1β in reserpine-treated mice.In addition,we showed that BoNT/A(0.1 U/mL)ameliorated reserpine-induced complement and microglia activation in mouse BV2 microglial cells in vitro.We conclude that BoNT/A ameliorates depressive-like behavior in a reserpine-induced PD mouse model through reversing the synapse loss mediated by classical complement induced-microglial engulfment as well as alleviating microglia-mediated proinflammatory responses.● Botulinum neurotoxin A ameliorates reserpine-induced depressive behaviors.● Complement activation is involved in the reserpine-induced mouse model.● Botulinum neurotoxin A reverses spine loss and reduced synapse density.● Botulinum neurotoxin A inhibits complement activation and microglial engulfment.● Botulinum neurotoxin A alleviates reserpine-induced neuroinflammation.

Parkinson's diseasedepressionreserpinebotulinum neurotoxin Amicrogliacomplement

Yang Li、Qiao Yin、Qi Li、An-ran Huo、Ting-ting Shen、Jia-qian Cao、Chun-feng Liu、Tong Liu、Wei-feng Luo、Qi-fei Cong

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Department of Neurology and Clinical Research Center of Neurological Disease,The Second Affiliated Hospital of Soochow University,Suzhou 215004,China

Department of Neurology,Huzhou Central Hospital,The Affiliated Huzhou Hospital,Zhejiang University School of Medicine,Huzhou 313000,China

institute of Neuroscience and Jiangsu Key Laboratory of Neuropsychiatric Diseases,Soochow University,Suzhou 215123,China

Institute of Pain Medicine and Special Environmental Medicine,Nantong University,Nantong 226019,China

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Second Affiliated Hospital of Soochow University国家自然科学基金江苏省自然科学基金Suzhou Medical and Health Technology Innovation Projectstartup fundingstartup fundingClinical Research Center of Neurological Disease in The Second Affiliated Hospital of Soochow UniversitySuzhou Science and Technology Plan Key Technology Application Research Project国家自然科学基金Suzhou Clinical Research Center of Neurological Disease江苏省自然科学基金江苏高校优势学科建设工程项目

32200778BK20220494SKY2022107NH21500221NH21500122ND2022A04SS201906081671270SZZX201503BK2011294

2023

10.1038/s41401-023-01058-x

中国药理学报(英文版)
中科院上海药物研究所

中国药理学报(英文版)

CSTPCDCSCD北大核心
影响因子：0.926
ISSN：1671-4083
年,卷(期)：2023.44(7)
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