Research Paper Advance Articles
Minocycline inhibition of microglial rescues nigrostriatal dopaminergic neurodegeneration caused by mutant alpha-synuclein overexpression
- 1 Department of Neurology, First Affiliated Hospital of Soochow University, Suzhou 215006, China
- 2 Affiliated First Clinical College of Xuzhou Medical University, Xuzhou 221004, China
- 3 Department of Geriatric Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221004, China
- 4 Department of Genetics, Xuzhou Medical University, Xuzhou 221004, China
- 5 Experimental Animal Center, Xuzhou Medical University, Xuzhou 221004, China
- 6 Deprtment of Physiology, Xuzhou Medical University, Xuzhou 221004, China
- 7 Department of Pathology, Xuzhou Medical University, Xuzhou 221004, China
- 8 Department of Neurology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, China
- 9 Public Experimental Research Center of Xuzhou Medical University, Xuzhou 221004, China
Received: February 7, 2020 Accepted: May 25, 2020 Published: July 24, 2020https://doi.org/10.18632/aging.103440
How to Cite
Copyright © 2020 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Studies indicate that mutant α-synuclein (mαSyn) is involved in the pathogenesis of Parkinson’s disease (PD). The mαSyn expression leads to the loss of dopaminergic neurons in the substantia nigra (SN) and consequent motor dysfunctions. Additionally, studies found that PD was accompanied by extensive neuroinflammation of SN. However, it remains unclear as to whether microglia participate in the mαSyn pathology. This issue is addressed by using AAV-mα-Syn (A30P-A53T) to overexpress the human mαSyn in the SN in view of establishing the PD model. Subsequently, minocycline (Mino) was used to inhibit microglia activity, and an interleukin-1 receptor (IL-1R1) antagonist was used to hinder the IL-1R1 function. Finally, immunohistochemistry was used to analyze phosphorylated αSyn (Ser129) and TH-positive cells in the SN. Dopamine levels were analyzed by high performance liquid chromatography. mαSyn overexpression in the SN induced motor dysfunction, decreased striatal dopamine levels, and increased pathological αSyn 12 weeks after AAV injection. The data demonstrated that inhibiting microglial activation or hindering IL-1R1 reversed the persistent motor deficits, neurodegeneration of the nigrostriatal dopaminergic system, and development of Lewy body pathology caused by human mαSyn overexpression in the SN. Additionally, these findings indicate that neuroinflammation promotes the loss of neuronal cells.