Activation and polarization of striatal microglia and astrocytes are involved in bradykinesia and allodynia in early-stage parkinsonian mice  

作　　者：Xue Zhang Zi-Lin Shen Ya-Wei Ji Cui Yin Cheng Xiao Chunyi Zhou 

机构地区：[1]Jiangsu Province Key Laboratory of Anesthesiology,School of Anesthesiology,Xuzhou Medical University,Xuzhou 221004,China [2]Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology,Xuzhou Medical University,Xuzhou 221004,China [3]NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs,School of Anesthesiology,Xuzhou Medical University,Xuzhou 221004,China

出　　处：《Fundamental Research》2024年第4期806-819,共14页自然科学基础研究（英文版）

基　　金：the National Natural Science Foundation of China(81971038,82071231,82171235,82271293,81870891);the Fund for Jiangsu Province Specially-Appointed Professor(C.X.,C.Z.);the Natural Science Foundation of Jiangsu Province(BK20211349);the Leadership Program in Xuzhou Medical University(JBGS202203).

摘　　要：In addition to the cardinal motor symptoms,pain is a major non-motor symptom of Parkinson's disease(PD).Neuroinflammation in the substantia nigra pars compacta and dorsal striatum is involved in neurodegeneration in PD.But the polarization of microglia and astrocytes in the dorsal striatum and their contribution to motor deficits and hyperalgesia in PD have not been characterized.In the present study,we observed that hemiparkinsonian mice established by unilateral 6-OHDA injection in the medial forebrain bundle exhibited motor deficits and mechanical allodynia.In these mice,both microglia and astrocytes in the dorsal striatum were activated and polarized to M1/M2 microglia and A1/A2 astrocytes as genes specific to these cells were upregulated.These effects peaked 7 days after 6-OHDA injection.Meanwhile,striatal astrocytes in parkinsonian mice also displayed hyperpolarized membrane potentials,enhanced voltage-gated potassium currents,and dysfunction in inwardly rectifying potassium channels and glutamate transporters.Systemic administration of minocycline,a microglia inhibitor,attenuated the expression of genes specific to M1 microglia and A1 astrocytes in the dorsal striatum(but not those specific to M2 microglia and A2 astrocytes),attenuated the damage in the nigrostriatal dopaminergic system,and alleviated the motor deficits and mechanical allodynia in parkinsonian mice.By contrast,local administration of minocycline into the dorsal striatum of parkinsonian mice mitigated only hyperalgesia.This study suggests that M1 microglia and A1 astrocytes in the dorsal striatum may play important roles in the development of pathophysiology underlying hyperalgesia in the early stages of PD.

关 键 词：Parkinson's disease Dopaminergic system STRIATUM MICROGLIA ASTROCYTES Substantia nigra pars compacta 

分 类 号：R742.5[医药卫生—神经病学与精神病学]