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Microglial Prrc2a regulates microglia-neuron interaction in cerebellum and motor functions in mice
Xiaoheng Li1, Pin Yang1,2, Binbin Dong3
1The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing 100850, China.
Abstract:
The crosstalk between microglia and neuron has been recognized as a crucial process in the development and disorders of the central nervous system. The present study probes into the role of Prrc2a-a post-transcriptional regulator that binds and stabilizes transcripts pivotal for microglial development-specifically within cerebellar microglia using a microglia-targeted conditional knockout model, identifying it as a crucial regulator of microglial function. Single-cell RNA sequencing underscored a transcriptomic shift in Prrc2a-ablated microglia, revealing an abnormally activated state. Prrc2a deficiency and the consequent alteration of cerebellar microglia were associated with reduced mutual interactions, altered Purkinje cell morphology and electrophysiological activity, decreased molecular layer width, and subsequently defects in motor balance and coordination. Collectively, this study provides insights into the molecular mechanisms underlying microglia-neuron interaction within the cerebellum.
Insights
Prrc2a is vital for cerebellar microglial function and neuron interaction. Its deficiency causes abnormal microglia activation, leading to motor deficits and altered brain structure.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Microglia-neuron crosstalk is essential for central nervous system development and function.
- Post-transcriptional regulation plays a key role in microglial development and activation.
Purpose of the Study:
- To investigate the role of Prrc2a, a post-transcriptional regulator, in cerebellar microglia.
- To understand how Prrc2a deficiency impacts microglia-neuron interactions and motor behavior.
Main Methods:
- Utilized a microglia-targeted conditional knockout mouse model to ablate Prrc2a.
- Performed single-cell RNA sequencing to analyze transcriptomic changes in Prrc2a-deficient microglia.
- Assessed Purkinje cell morphology, electrophysiology, and motor function.
Main Results:
- Prrc2a ablation led to transcriptomic shifts and an abnormally activated state in cerebellar microglia.
- Prrc2a deficiency resulted in reduced microglia-neuron interactions, altered Purkinje cell activity, and decreased molecular layer width.
- Mice with Prrc2a-deficient microglia exhibited motor balance and coordination defects.
Conclusions:
- Prrc2a is a critical regulator of cerebellar microglial function.
- Prrc2a deficiency disrupts microglia-neuron communication, impacting cerebellar structure and motor control.
- This study elucidates molecular mechanisms underlying microglia-neuron interactions in the cerebellum.

