Dysfunctional Glutamatergic and γ-Aminobutyric Acidergic Activities in Prefrontal Cortex of Mice in Social Defeat Model of Depression

Pandichelvam Veeraiah, Judith Miriam Noronha, Swati Maitra, Puneet Bagga, Nitin Khandelwal, Sumana Chakravarty, Arvind Kumar, Anant B. Patel

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

Background Depression is a complex neuropsychiatric syndrome that is often very severe and life threatening. In spite of the remarkable progress in understanding the neural biology, the etiopathophysiology of depression is still elusive. In this study, we have investigated molecular mechanisms in the prefrontal cortex of mice showing depression-like phenotype induced by chronic defeat stress. Methods Depression-like phenotype was induced in C57BL/6 mice by subjecting them to a 10-day social defeat paradigm. The metabolic activity of excitatory (glutamatergic) and inhibitory (γ-aminobutyric acid [GABA]ergic) neurons of the prefrontal cortex was measured by 1H-[13C]-nuclear magnetic resonance spectroscopy together with infusion of [1,6-13C2]glucose. In addition, the expression level of genes associated with glutamatergic and GABAergic pathways was monitored by quantitative polymerase chain reaction. Results Mice showing depression-like phenotype exhibit significant reduction in the levels of glutamate, glutamine, N-acetyl aspartate, and taurine in the prefrontal cortex. Most importantly, findings of reduced 13C labeling of glutamate-C4, glutamate-C3, and GABA-C2 from [1,6-13C2]glucose indicate decreased glutamatergic and GABAergic neuronal metabolism and neurotransmitter cycling in the depressed mice. The reduced glutamine-C4 labeling suggests decreased neurotransmitter cycling in depression. Quantitative polymerase chain reaction analysis revealed reduced transcripts of Gad1 and Eaat2 genes, which code for enzymes involved in the synthesis of GABA and the clearance of glutamate from synapses, respectively. Conclusions These data indicate that the activities of glutamatergic and GABAergic neurons are reduced in mice showing a depression-like phenotype, which is supported by molecular data for the expression of genes involved in glutamate and GABA pathways.

Original languageEnglish (US)
Pages (from-to)231-238
Number of pages8
JournalBiological Psychiatry
Volume76
Issue number3
DOIs
StatePublished - Aug 1 2014
Externally publishedYes

Keywords

  • Brain
  • cerebral metabolism
  • gene expression
  • glia
  • mood disorders
  • NMR spectroscopy

ASJC Scopus subject areas

  • Biological Psychiatry

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