A pivotal role of nonmuscle myosin II during microglial activation

Area of Science:

• Neuroscience
• Cell Biology
• Immunology

Background:

• Microglia, the resident macrophages of the central nervous system (CNS), are key players in CNS inflammation.
• Activated microglia undergo significant cellular changes, including migration, phagocytosis, and mediator release, to respond to brain damage.
• Nonmuscle myosin II (NM II) is a critical cytoskeletal component involved in cellular rearrangements in nonmuscle cells.

Purpose of the Study:

• To investigate the functional role of NM II in both resting and activated microglia.
• To determine NM II's involvement in microglial morphology, migration, and phagocytosis.

Main Methods:

• Immunohistochemistry was used to detect NM II isoform B (NM IIB) expression in microglia during cuprizone-induced demyelination and in cultured microglia.
• The NM II inhibitor blebbistatin was employed to assess its effects on microglial function.
• Changes in cell morphology, chemokine-directed migration, phagocytosis, NM IIB distribution, actin patterning, nitric oxide (NO), and TNFα secretion were analyzed.

Main Results:

• Strong expression of NM IIB was observed in activated microglia in vivo and in vitro.
• Blebbistatin treatment impaired microglial morphological shaping, chemokine-directed migration, and phagocytosis.
• NM II inhibition altered NM IIB redistribution and actin microfilament organization, attenuated nitric oxide release, but did not affect TNFα secretion.

Conclusions:

• Nonmuscle myosin II plays a pivotal role in cytoskeleton organization during microglial activation.
• Understanding NM II's function is vital for elucidating microglial mechanisms in inflammatory CNS diseases.