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Chronic corticosterone administration down-regulates metabotropic glutamate receptor 5 protein expression in the rat
A H Iyo1, A M Feyissa, A Chandran
1Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
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.
Insights
Chronic stress, indicated by elevated corticosterone, reduces metabotropic glutamate receptor 5 (mGluR5) protein in rat hippocampus. This finding links stress hormones to glutamate system dysfunction relevant to major depressive disorder (MDD).
Area of Science:
- Neuroscience
- Molecular Psychiatry
- Glutamatergic System
Background:
- Major depressive disorder (MDD) is associated with glutamate system dysfunction.
- Previous studies reported reduced metabotropic glutamate receptor subtype 5 (mGluR5) in MDD postmortem brains.
- The neurobiological mechanisms underlying these mGluR5 abnormalities remain unclear.
Purpose of the Study:
- To investigate the effect of chronic corticosterone (CORT) administration on mGluR5 expression in rat brain.
- To explore the potential role of elevated glucocorticoids in MDD-related glutamate dysregulation.
Main Methods:
- Adult male rats received daily subcutaneous injections of CORT (40 mg/kg) or vehicle for 21 days.
- mGluR5 protein and mRNA levels were quantified in the frontal cortex and hippocampus using Western blotting and qPCR.
- mGluR1 protein levels were also assessed.
Main Results:
- Chronic CORT administration significantly reduced mGluR5 protein expression in the hippocampus by 27% (P=0.0006).
- Hippocampal mGluR5 mRNA levels, and mGluR5 expression in the frontal cortex (both mRNA and protein), remained unchanged.
- mGluR1 protein levels were unaffected in both brain regions.
Conclusions:
- Chronic exposure to elevated corticosterone levels regulates mGluR5 protein expression in the rat hippocampus.
- These findings suggest that increased glucocorticoid levels may contribute to impaired glutamate neurotransmission observed in MDD.
- The study provides a potential animal model mechanism for reduced mGluR5 observed in human MDD studies.
