Kainate induces rapid redistribution of the actin cytoskeleton in ameboid microglia.
Microglia are key mediators of the immune response in the central nervous system (CNS). They are closely related to macrophages and undergo dramatic morphological and functional changes after CNS trauma or excitotoxic lesions. Microglia can be directly stimulated by excitatory neurotransmitters and are known to express many neurotransmitter receptors. The role of these receptors, however, is not clear. This study describes the microglial response to the glutamate receptor agonist kainate (KA) and shows via immunochemistry that the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-type glutamate receptor subunit GluR1 is present on cultured microglia. In the presence of 100 microM or 1 mM KA, cultured microglia underwent dramatic morphological and cytoskeletal changes as observed by time-lapse photography and quantitative confocal analysis of phalloidin labeling. KA-stimulated microglia showed condensation of cytoplasmic actin filaments, rapid de- and repolymerization, and cytoplasmic redistribution of condensed actin bundles. Rearrangement of actin filaments-thought to be involved in locomotion and phagocytosis and to indicate an increased level of activation (for reviews see Greenberg [ 1995] Trends Cell Biol. 5:93-99; Imai and Kohsaka [ 2002] Glia 40:164-174)-was significantly increased in treated vs. control cultures. Morphological plasticity and membrane ruffling were also seen. These findings suggest direct microglial excitation via glutamate receptor pathways. Thus, neurotransmitter release after brain or spinal cord injury might directly modulate the inflammatory response.
Christensen
Randolph N
RN
Department of Neuroscience, The Ohio State University, Columbus, Ohio 43210, USA.
Ha
Byeong Keun
BK
Sun
Fang
F
Bresnahan
Jacqueline C
JC
Beattie
Michael S
MS
D000199:Actins / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D018920:Coculture Techniques / Q000379:methods; D003599:Cytoskeleton / Q000187:drug effects*; D003952:Diagnostic Imaging / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D007608:Kainic Acid / Q000494:pharmacology*; D037102:Lectins / Q000378:metabolism; D017628:Microglia / Q000166:cytology / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D018091:Receptors, AMPA / Q000378:metabolism; D013997:Time Factors
D000199:Actins; D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D007608:Kainic Acid; D037102:Lectins; D018091:Receptors, AMPA