Partial depletion and repopulation of microglia have different effects in the acute MPTP mouse model of Parkinson’s disease

Abstract

Objectives Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive and selective degeneration of dopaminergic neurons. Microglial activation and neuroinflammation are associated with the pathogenesis of PD. However, the relationship between microglial activation and PD pathology remains to be explored. Materials and Methods An acute regimen of MPTP was administered to adult C57BL/6J mice with normal, much reduced or repopulated microglial population. Damages of the dopaminergic system were comprehensively assessed. Inflammation‐related factors were assessed by quantitative PCR and Multiplex immunoassay. Behavioural tests were carried out to evaluate the motor deficits in MPTP‐challenged mice. Results The receptor for colony‐stimulating factor 1 inhibitor PLX3397 could effectively deplete microglia in the nigrostriatal pathway of mice via feeding a PLX3397‐formulated diet for 21 days. Microglial depletion downregulated both pro‐inflammatory and anti‐inflammatory molecule expression at baseline and after MPTP administration. At 1d post‐MPTP injection, dopaminergic neurons showed a significant reduction in PLX3397‐fed mice, but not in control diet (CD)‐fed mice. However, partial microglial depletion in mice exerted little effect on MPTP‐induced dopaminergic injuries compared with CD mice at later time points. Interestingly, microglial repopulation brought about apparent resistance to MPTP intoxication. Conclusions Microglia can inhibit PD development at a very early stage; partial microglial depletion has little effect in terms of the whole process of the disease; and microglial replenishment elicits neuroprotection in PD mice.

Neuroprotective Effects of Sodium Butyrate and Monomethyl Fumarate Treatment through GPR109A Modulation and Intestinal Barrier Restoration on PD Mice

“…The majority of clinical symptoms can therefore be mimicked by MPTP, particularly motor dysfunctional symptoms such as tremors and bradykinesia [ 55 ]. Acute, chronic, and subacute regimens are the three types of regimens avail for the creation of PD models by MPTP [ 27 , 48 , 56 , 57 ]. The subacute regimen is the most popular of these three model techniques due to its security and effectiveness.…”

Deficiency of miR-29b2/c leads to accelerated aging and neuroprotection in MPTP-induced Parkinson’s disease mice

“…The methods of RNA and miRNA extraction, reverse transcription, and qPCR were referred to our previous work [ 24 , 45 ]. The primers for qPCR were listed in Table 1 .…”

Prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior

“…In our mouse model, the partial depletion of microglia from the neonatal brain before prolonged exposure to sevoflurane and later microglia repopulation can ameliorate sevoflurane-induced anxiety-like behavior in adulthood. Microglial depletion and repopulation have also shown impressive results in some animal models of neurological diseases and deficits, including traumatic brain injury, maternal immune activation-induced repetitive behavior, social deficits, and Parkinson's disease (54)(55)(56)(57). These results support continuing research into the potential of microglial depletion and repopulation for treating neurological disorders and deficits.…”