Heterogeneity of the astrocytic AMPA-receptor transcriptome

Glia. 2018 Dec;66(12):2604-2616. doi: 10.1002/glia.23514. Epub 2018 Oct 28.

Abstract

Astrocytes form the largest class of glial cells in the central nervous system. They serve plenty of diverse functions that range from supporting the formation and proper operation of synapses to controlling the blood-brain barrier. For many of them, the expression of ionotropic glutamate receptors of the AMPA subtype (AMPARs) in astrocytes is of key importance. AMPARs form as macromolecular protein complexes, whose composition of the pore-lining GluA subunits and of an extensive set of core and peripheral complex constituents defines both their trafficking and gating behavior. Although astrocytic AMPARs have been reported to exhibit heterogeneous properties, their molecular composition is largely unknown. In this study, we sought to quantify the astrocytic AMPAR transcriptome during brain development and with respect to selected brain regions. Whereas the early postnatal pattern of AMPAR mRNA expression showed minor variation over time, it did show significant heterogeneity in different brain regions. Cerebellar astrocytes express a combination of AMPAR complex constituents that is remarkably distinct from the one in neocortical or hippocampal astrocytes. Our study provides a workflow and a first reference for future investigations into the molecular and functional diversity of glial AMPARs.

Keywords: AMPA; astrocytes; fluorescence activated cell sorting; heterogeneous composition; ionotropic glutamate receptors; quantitative real-time PCR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antigens / genetics
  • Antigens / metabolism
  • Astrocytes / metabolism*
  • Astrocytes / ultrastructure
  • Brain / cytology
  • Brain / growth & development
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Excitatory Amino Acid Transporter 1 / metabolism
  • Gene Expression Regulation, Developmental / genetics*
  • Glial Fibrillary Acidic Protein / metabolism
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Membrane Potentials / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Oligodendrocyte Transcription Factor 2 / metabolism
  • Patch-Clamp Techniques
  • Proteoglycans / genetics
  • Proteoglycans / metabolism
  • Receptors, AMPA / genetics*
  • Receptors, AMPA / metabolism*
  • SOXE Transcription Factors / genetics
  • SOXE Transcription Factors / metabolism
  • Transcriptome / physiology*
  • Xenopus laevis

Substances

  • Aif1 protein, mouse
  • Antigens
  • Calcium-Binding Proteins
  • Excitatory Amino Acid Transporter 1
  • Glial Fibrillary Acidic Protein
  • Microfilament Proteins
  • Olig2 protein, mouse
  • Oligodendrocyte Transcription Factor 2
  • Proteoglycans
  • Receptors, AMPA
  • SOXE Transcription Factors
  • Slc1a3 protein, mouse
  • Sox10 protein, mouse
  • chondroitin sulfate proteoglycan 4
  • Green Fluorescent Proteins