Basal astrocyte and microglia activation in the central nervous system of Familial Hemiplegic Migraine Type I mice

Magni, G.; Boccazzi, M.; Bodini, A.; Abbracchio, M.P.; Maagdenberg, A.M.J.M. van den; Ceruti, S.

doi:doi:10.1177/0333102419861710

Background Gain-of-function missense mutations in the alpha(1A) subunit of neuronal Ca(V)2.1 channels, which define Familial Hemiplegic Migraine Type 1 (FHM1), result in enhanced cortical glutamatergic transmission and a higher susceptibility to cortical spreading depolarization. It is now well established that neurons signal to surrounding glial cells, namely astrocytes and microglia, in the central nervous system, which in turn become activated and in pathological conditions can sustain neuroinflammation. We and others previously demonstrated an increased activation of pro-algogenic pathways, paralleled by augmented macrophage infiltration, in both isolated trigeminal ganglia and mixed trigeminal ganglion neuron-satellite glial cell cultures of FHM1 mutant mice. Hence, we hypothesize that astrocyte and microglia activation may occur in parallel in the central nervous system. Methods We have evaluated signs of reactive glia in brains from naive FHM1 mutant mice in comparison with...Show moreBackground Gain-of-function missense mutations in the alpha(1A) subunit of neuronal Ca(V)2.1 channels, which define Familial Hemiplegic Migraine Type 1 (FHM1), result in enhanced cortical glutamatergic transmission and a higher susceptibility to cortical spreading depolarization. It is now well established that neurons signal to surrounding glial cells, namely astrocytes and microglia, in the central nervous system, which in turn become activated and in pathological conditions can sustain neuroinflammation. We and others previously demonstrated an increased activation of pro-algogenic pathways, paralleled by augmented macrophage infiltration, in both isolated trigeminal ganglia and mixed trigeminal ganglion neuron-satellite glial cell cultures of FHM1 mutant mice. Hence, we hypothesize that astrocyte and microglia activation may occur in parallel in the central nervous system. Methods We have evaluated signs of reactive glia in brains from naive FHM1 mutant mice in comparison with wild type animals by immunohistochemistry and Western blotting. Results Here we show for the first time signs of reactive astrogliosis and microglia activation in the naive FHM1 mutant mouse brain. Conclusions Our data reinforce the involvement of glial cells in migraine, and suggest that modulating such activation may represent an innovative approach to reduce pathology.Show less

Leiden University Scholarly Publications

View statistics

In Collections

Basal astrocyte and microglia activation in the central nervous system of Familial Hemiplegic Migraine Type I mice