Reduced expression of glutamate transporters vGluT1, EAAT2 and EAAT4 in learned helpless rats, an animal model of depression

Zink, M., Vollmayr, B., Gebicke-Haerter, P. J., Henn, F. A. (February 2010) Reduced expression of glutamate transporters vGluT1, EAAT2 and EAAT4 in learned helpless rats, an animal model of depression. Neuropharmacology, 58 (2). pp. 465-73. ISSN 0028-3908

DOI: 10.1016/j.neuropharm.2009.09.005


BACKGROUND: It has been widely accepted that glial pathology and disturbed synaptic transmission contribute to the neurobiology of depression. Apart from monoaminergic alterations, an influence of glutamatergic signal transduction has been reported. Therefore, gene expression of glutamate transporters that strictly control synaptic glutamate concentrations have to be assessed in animal models of stress and depression. METHODS: We performed in situ-hybridizations in learned helplessness rats, a well established animal model of depression, to assess vGluT1 and EAAT1-4. Sprague-Dawley rats of two inbred lines were tested for helpless behavior and grouped into three cohorts according to the number of failures to stop foot shock currents by lever pressing. RESULTS: Helpless animals showed a significantly suppressed expression of the glial glutamate transporter EAAT2 (rodent nomenclature GLT1) in hippocampus and cerebral cortex compared to littermates with low failure rate and not helpless animals. This finding was validated on protein level using immunohistochemistry. Additionally, expression levels of EAAT4 and the vesicular transporter vGluT1 were reduced in helpless animals. In contrast, the transcript levels of EAAT1 (GLAST) and EAAT3 (EAAC1) were not significantly altered. CONCLUSIONS: These results strongly suggest reduced astroglial glutamate uptake and implicate increased glutamate levels in learned helplessness. The findings are in concert with antidepressant effects of NMDA-receptor antagonists and the hypotheses that impaired astroglial functions contribute to the pathogenesis of affective disorders.

Item Type: Paper
Uncontrolled Keywords: Animals Brain/*metabolism Cerebral Cortex/metabolism Depressive Disorder/*metabolism Disease Models, Animal Excitatory Amino Acid Transporter 1/metabolism Excitatory Amino Acid Transporter 2/*metabolism Excitatory Amino Acid Transporter 3/metabolism Excitatory Amino Acid Transporter 4/*metabolism *Helplessness, Learned Hippocampus/metabolism Male Rats Rats, Inbred Strains Rats, Sprague-Dawley Vesicular Glutamate Transport Protein 1/*metabolism
Subjects: diseases & disorders > mental disorders > mood disorders > depression
bioinformatics > genomics and proteomics > small molecules > Glutamate
organism description > animal > mammal > rodent > rat
organism description > animal > mammal > rodent > rat
CSHL Authors:
Communities: CSHL labs > Henn lab
Depositing User: Matt Covey
Date: February 2010
Date Deposited: 06 Jun 2014 19:00
Last Modified: 06 Jun 2014 19:00
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