Astrocytes facilitate gabazine-evoked electrophysiological hyperactivity and distinct biochemical responses in mature neuronal cultures

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the adult brain that binds to GABA receptors and hyperpolarizes the postsynaptic neuron. Gabazine acts as a competitive antagonist to type A GABA receptors (GABAAR), thereby causing diminished neuronal hyperpolarization and GABAAR-mediated inhibition. However, the biochemical effects and the potential regulatory role of astrocytes in this process remain poorly understood. To address this, we investigated the neuronal responses of gabazine in rat cortical cultures containing varying ratios of neurons and astrocytes. Electrophysiological characterization was performed utilizing microelectrode arrays (MEAs) with topologically controlled microcircuit cultures that enabled control of neuronal network growth. Biochemical analysis of the cultures was performed using traditional dissociated cultures on coverslips. Our study indicates that, upon gabazine stimulation, astrocyte-rich neuronal cultures exhibit elevated electrophysiological activity and tyrosine phosphorylation of tropomyosin receptor kinase B (TrkB; receptor for brain-derived neurotrophic factor), along with distinct cytokine secretion profiles. Notably, neurons lacking proper astrocytic support were found to experience synapse loss and decreased mitogen-activated protein kinase (MAPK) phosphorylation. Furthermore, astrocytes contributed to neuronal viability, morphology, vascular endothelial growth factor (VEGF) secretion, and overall neuronal network functionality, highlighting the multifunctional role of astrocytes. (Figure presented.)

Original languageEnglish
Pages (from-to)3076-3094
JournalJournal of Neurochemistry
Volume168
Issue number9
Early online date2024
DOIs
Publication statusPublished - Sept 2024
Publication typeA1 Journal article-refereed

Keywords

  • co-culture
  • gabazine
  • gamma-aminobutyric acid
  • microelectrode array
  • TrkB

Publication forum classification

  • Publication forum level 2

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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