Microglia depletion reduces neurodegeneration and remodels extracellular matrix in a mouse Parkinson’s disease model triggered by α-synuclein overexpression

npj Parkinson s Disease, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 9, 2025

Chronic neuroinflammation with sustained microglial activation occurs in Parkinson's disease (PD), yet the mechanisms and exact contribution of these cells to neurodegeneration remains poorly understood. In this study, we induced progressive dopaminergic neuron loss mice via rAAV-hSYN injection cause neuronal expression α-synuclein, which produced behavioral alterations. We administered PLX5622, a colony-stimulating factor 1 receptor inhibitor, for 3 weeks prior injection, maintaining it 8 eliminate microglia. This chronic treatment paradigm prevented development motor deficits concomitantly preserved cell weakened α-synuclein phosphorylation. Gene profiles related extracellular matrix (ECM) remodeling were increased after microglia depletion PD mice, further validated on protein level. demonstrated that exert adverse effects during α-synuclein-overexpression-induced lesion formation, their remodels ECM aids recovery following insult.

Language: Английский

Investigation in the cannabigerol derivative VCE-003.2 as a disease-modifying agent in a mouse model of experimental synucleinopathy

Behavioral and Brain Functions, Journal Year: 2024, Volume and Issue: 20(1)

Published: Nov. 1, 2024

The cannabigerol derivative VCE-003.2, which has activity at the peroxisome proliferator-activated receptor-γ afforded neuroprotection in experimental models of Parkinson's disease (PD) based on mitochondrial dysfunction (6-hydroxydopamine-lesioned mice) and neuroinflammation (LPS-lesioned mice). Now, we aim to explore VCE-003.2 neuroprotective properties a PD model that also involves protein dysregulation, other key event pathogenesis.

Language: Английский