Effects Of Ketamine On Astrocyte And Microglia In Parkinson's Disease Mice Induced By MPTP

BACKGROUND:Parkinson's disease(PD)is a common neurodegenerative disease.Its symptoms include resting tremor,bradykinesia,unstable posture,and depression.The pathological feature of PD is the progressive loss of dopaminergic neurons.Its pathophysiology involves multiple pathways and mechanisms,including neuroinflammation,glial cell activation,oxidative stress,endoplasmic reticulum stress,and mitochondrial dysfunction,and so on.However,more and more evidence showed that microglial activation and astrocyte proliferation played an important role in the occurrence and development of PD.Ketamine as a non-competitive glutamate N-methyl-D-aspartate(NMDA)receptor inhibitor has anti-inflammatory,anti-depressant,and neuroprotective effects.Clinical studies have also found that ketamine has a certain relief effect on the motor symptoms of PD patients.This experiment explores the effect of ketamine on PD astrocytes and microglia by constructing a PD mouse model.AIM:To investigate the effects of Ketamine at subanesthetic dose on astrocyte and microglia in PD mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).METHODS:36 Healthy male C57BL/6 mice were randomly divided into three groups(12 mice per group): Na Cl group(intraperitoneal injection of saline),MPTP group(intraperitoneal injection of MPTP)and Ketamine group(intraperitoneal injection of MPTP and Ketamine).The behavioral differences among the mice in three groups were examined by Tail suspension test,Gait analysis test and Rotarod test.Immunofluorescence staining and Western blot were used to detect the expression of glial fibrillary acidic protein(GFAP),ionized calcium binding adapter molecule 1(Iba1),aspartate-specific cysteinyl proteinase 3(caspase-3),myocyte enhancer factor 2D(MEF2D)and ?-synuclein in substantia nigra(SN),caudate putamen(CP)and visual cortex(CX).RESULTS:According to the results of Tail suspension test,Gait analysis test and Rotarod test;MPTP group mice showed an increased duration of immobility,a shortened step length and a decreased duration of running compared to Na Cl group mice.While Ketamine group mice showed a decreased duration of immobility,an expanded step length and an increased duration of running compared to MPTP group mice.According to the results of Immunofluorescence staining and Western blot,compared with the Na Cl group,in SN,CP and CX,MPTP group mice showed a reduced branch number and total branch length of microglia,an increased expression of GFAP,caspase-3,?-synuclein,a decreased expression of MEF2 D.While,compared to MPTP group mice,Ketamine group mice showed an increased branch number and total branch length of microglia,a decreased expression of GFAP,caspase-3,?-synuclein,an increased expression of MEF2 D.CONCLUSION:Ketamine at subanesthetic dose can inhibit the proliferation of astrocyte and the activation of microglia in MPTP induced PD mice.