Chronic corticosterone administration down-regulates metabotropic glutamate receptor 5 protein expression in the rat hippocampus

A. H. Iyo, Anteneh Feyissa, A. Chandran, M. C. Austin, S. Regunathan, B. Karolewicz

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Several lines of evidence suggest a dysfunctional glutamate system in major depressive disorder (MDD). Recently, we reported reduced levels of metabotropic glutamate receptor subtype 5 (mGluR5) in postmortem brains in MDD, however the neurobiological mechanisms that induce these abnormalities are unclear. In the present study, we examined the effect of chronic corticosterone (CORT) administration on the expression of mGluR5 protein and mRNA in the rat frontal cortex and hippocampus. Rats were injected with CORT (40 mg/kg s.c.) or vehicled once daily for 21 days. The expression of mGluR5 protein and mRNA was assessed by Western blotting and quantitative real-time PCR (qPCR). In addition, mGluR1 protein was measured in the same animals. The results revealed that while there was a significant reduction (-27%, P=0.0006) in mGluR5 protein expression in the hippocampus from CORT treated rats, mRNA levels were unchanged. Also unchanged were mGluR5 mRNA and protein levels in the frontal cortex and mGluR1 protein levels in both brain regions. Our findings provide the first evidence that chronic CORT exposure regulates the expression of mGluR5 and are in line with previous postmortem and imaging studies showing reduced mGluR5 in MDD. Our findings suggest that elevated levels of glucocorticoids may contribute to impairments in glutamate neurotransmission in MDD.

Original languageEnglish (US)
Pages (from-to)1567-1574
Number of pages8
JournalNeuroscience
Volume169
Issue number4
DOIs
StatePublished - Sep 1 2010
Externally publishedYes

Fingerprint

Metabotropic Glutamate 5 Receptor
Corticosterone
Hippocampus
Down-Regulation
Major Depressive Disorder
Proteins
Messenger RNA
Frontal Lobe
Glutamic Acid
Brain
Synaptic Transmission
Glucocorticoids
Real-Time Polymerase Chain Reaction
Western Blotting

Keywords

  • Corticosterone
  • Frontal cortex
  • Hippocampus
  • Metabotropic glutamate receptor 1
  • Metabotropic glutamate receptor 5
  • Rat

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Chronic corticosterone administration down-regulates metabotropic glutamate receptor 5 protein expression in the rat hippocampus. / Iyo, A. H.; Feyissa, Anteneh; Chandran, A.; Austin, M. C.; Regunathan, S.; Karolewicz, B.

In: Neuroscience, Vol. 169, No. 4, 01.09.2010, p. 1567-1574.

Research output: Contribution to journalArticle

Iyo, A. H. ; Feyissa, Anteneh ; Chandran, A. ; Austin, M. C. ; Regunathan, S. ; Karolewicz, B. / Chronic corticosterone administration down-regulates metabotropic glutamate receptor 5 protein expression in the rat hippocampus. In: Neuroscience. 2010 ; Vol. 169, No. 4. pp. 1567-1574.
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