Enhanced Microglial Engulfment of Dopaminergic Synapses Induces Parkinson's Disease-Related Executive Dysfunction in an Acute LPC Infusion Targeting the mPFC.

ABSTRACT: The dysfunction of the dopaminergic projection from the ventral tegmental area (VTA) to the medial prefrontal cortex (mPFC) is believed to play a key role in the pathophysiology of Parkinson's disease (PD) accompanied by executive dysfunction (EDF). In this study, we identified an abnormal increase in lysophosphatidylcholine (LPC) levels in PD patients, which closely correlates with the severity of cognitive impairment. LPC disrupts the miR-2885/TDP-43 signaling pathway in microglia, driving dopaminergic presynaptic engulfment. In LPC-exposed mice, microglial activation via miR-2885/TDP-43/p65 signaling led to inflammatory cytokine and complement release, marking dopaminergic synapses for phagocytosis with a "PS/C1q" signal. Following the inhibition of LPC-induced microglial activation thr

SUBMITTER: Liu Y 

PROVIDER: S-EPMC12073916 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature