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

Cephalalgia. 2019 Dec;39(14):1809-1817. doi: 10.1177/0333102419861710. Epub 2019 Jul 1.


Background: Gain-of-function missense mutations in the α1A subunit of neuronal CaV2.1 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 naïve 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 naïve 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.

Keywords: Reactive astrocytes; activated microglia; migraine; neuroinflammation.

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Central Nervous System / metabolism*
  • Cerebellar Ataxia / genetics*
  • Cerebellar Ataxia / metabolism*
  • Gene Knock-In Techniques
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Microglia / metabolism*
  • Migraine Disorders / genetics*
  • Migraine Disorders / metabolism*
  • Random Allocation
  • Trigeminal Ganglion / metabolism

Supplementary concepts

  • Hemiplegic migraine, familial type 1