Microglial depletion exacerbates motor impairment and dopaminergic neuron loss in a 6-OHDA model of Parkinson's disease

Abstract

6-hydroxydopamine (6-OHDA) is a common neurotoxin used to induce Parkinson's disease (PD) in mice, exerting neurotoxic effects through the production of reactive oxygen species and microglial activation. However, the role of microglia in PD is still not clear, with contradictory reports showing neuroprotection or exacerbation of neuronal death. Microglial depletion aggravates motor coordination impairments and reduces tyrosine hydroxylase positive neurons in the substantia nigra pars compacta. Moreover, MeCP2 and Adora1 genes expression were downregulated, suggesting they may be involved in the neurodegenerative process. This study highlights that microglia plays a protective role in dopaminergic neuron survival during the initial phase of PD, and the investigation of the mechanisms of this effect in future studies will help elucidate the pathophysiology of PD.

Keywords: 6-OHDA; CSF1R inhibitor; Microglia depletion; Parkinson's disease.