Glia mechanisms in mood regulation: A novel model of mood disorders

Younglim Lee, Denise Gaskins, Amit Anand, Anantha Shekhar

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Introduction: Recent evidence in clinical and preclinical studies has implicated glutamate neurotransmissions in pathophysiology of mood disorders. The regulation of amino acid neurotransmission, i.e., glutamate and gamma-aminobutyric acid (GABA) involves coordinated mechanisms of uptake and transport within a tripartite synaptic system that includes neurons and glia. Newly appreciated role of the glia, more specifically astrocytes on neuronal functions combined with reported postmortem abnormalities of glia in patients with mood disorders further supports the role of glia in mood disorders. Materials and methods: This report presents some of our preliminary results utilizing glia-selective toxins and other pharmacological tools to suppress glial function within the limbic system to study the resulting behavioral abnormalities, and thus, elucidate glial involvement in the development of mood disorders. Results and discussion: We demonstrate that chronic blockade of glutamate uptake by a glial/neuronal transporter antagonist l-trans-pyrrolidine- 2,4-dicarboxylic acid (PDC) within the amygdala, a key area implicated in mood regulation, results in dose-dependent reduction in social exploratory behavior and disrupts circadian activity patterns consistent with symptoms of mood disorders. Similarly, the selective astrocytic glutamate transporter type 1 (GLT-1) blocker dihydrokainic acid (DHK) injected into the amygdala also results in reduced social interaction that is blocked by selective glutamate N-methyl-d-aspartate (NMDA) type receptor antagonist AP5. The results are discussed in the context of glial and glutamate mechanisms in mood disorders and potential therapeutic avenues to address these mechanisms.

Original languageEnglish (US)
Pages (from-to)55-65
Number of pages11
JournalPsychopharmacology
Volume191
Issue number1
DOIs
StatePublished - Mar 1 2007

Keywords

  • Amygdala
  • Astrocytes
  • Circadian rhythm
  • Depression
  • NMDA

ASJC Scopus subject areas

  • Pharmacology

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