P2X4 receptor controls microglia activation and favors remyelination in autoimmune encephalitis

Alazne Zabala1, Nuria Vazquez-Villoldo1, Björn Rissiek2

  • 1Achucarro Basque Center for Neurosciences, CIBERNED and Departamento de Neurociencias, Universidad del País Vasco, Leioa, Spain.

Insights

Purinergic receptor P2X4 (P2X4R) plays a crucial role in regulating microglia responses during autoimmune inflammation. Modulating P2X4R with ivermectin promotes myelin repair and reduces disease severity in models of neuroinflammation.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia are key immune cells in the central nervous system, essential for inflammation and repair.
  • Understanding microglia's role in pathology is vital for developing regenerative strategies.
  • Purinergic receptor P2X4 (P2X4R) is implicated in immune cell function.

Purpose of the Study:

  • To investigate the role of P2X4R in microglia/macrophages during autoimmune inflammation.
  • To evaluate the therapeutic potential of P2X4R modulation in demyelinating diseases.

Main Methods:

  • Experimental autoimmune encephalomyelitis (EAE) model for autoimmune inflammation.
  • Lysolecithin-induced demyelination model for myelin repair assessment.
  • In vitro studies on oligodendrocyte differentiation.

Main Results:

  • P2X4R blockade worsened EAE, promoted pro-inflammatory microglia, and inhibited myelin phagocytosis.
  • P2X4R blockade halted oligodendrocyte differentiation and remyelination.
  • Ivermectin (IVM) treatment shifted microglia to an anti-inflammatory phenotype, enhanced myelin phagocytosis, and promoted remyelination, ameliorating EAE.
  • IVM treatment promoted remyelination in the lysolecithin model.

Conclusions:

  • P2X4R signaling critically modulates microglia/macrophage responses in neuroinflammation.
  • Ivermectin (IVM) emerges as a potential therapeutic agent for promoting myelin repair and treating demyelinating conditions.

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