Astrocytes in Atp1a2-deficient heterozygous mice exhibit hyperactivity after induction of cortical spreading depression

FEBS Open Bio. 2020 Jun;10(6):1031-1043. doi: 10.1002/2211-5463.12848. Epub 2020 Apr 23.

Abstract

The ATP1A2 coding α2 subunit of Na,K-ATPase, which is predominantly located in astrocytes, is a causative gene of familial hemiplegic migraine type 2 (FHM2). FHM2 model mice (Atp1a2tmCKwk/+ ) are susceptible to cortical spreading depression (CSD), which is profoundly related to migraine aura and headache. However, astrocytic properties during CSD have not been examined in FHM2 model mice. Using Atp1a2tmCKwk/+ crossed with transgenic mice expressing G-CaMP7 in cortical neurons and astrocytes (Atp1a2+/- ), we analyzed the changes in Ca2+ concentrations during CSD. The propagation speed of Ca2+ waves and the percentages of astrocytes with elevated Ca2+ concentrations in Atp1a2+/- were higher than those in wild-type mice. Increased percentages of astrocytes with elevated Ca2+ concentrations in Atp1a2+/- may contribute to FHM2 pathophysiology.

Keywords: Atp1a2; CSD; FHM2; G-CaMP7; astrocyte; calcium imaging; migraine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Calcium / analysis
  • Calcium / metabolism
  • Cations, Divalent / analysis
  • Cations, Divalent / metabolism
  • Cerebral Cortex / cytology
  • Cerebral Cortex / pathology*
  • Cortical Spreading Depression / genetics*
  • Disease Models, Animal
  • Female
  • Heterozygote
  • Humans
  • Intravital Microscopy
  • Mice
  • Mice, Transgenic
  • Microscopy, Fluorescence, Multiphoton
  • Migraine with Aura / genetics*
  • Migraine with Aura / pathology
  • Neurons / metabolism
  • Sodium-Potassium-Exchanging ATPase / deficiency*
  • Sodium-Potassium-Exchanging ATPase / genetics
  • Stereotaxic Techniques

Substances

  • Cations, Divalent
  • Atp1a2 protein, mouse
  • Sodium-Potassium-Exchanging ATPase
  • Calcium

Supplementary concepts

  • Hemiplegic migraine, familial type 2