Stress-induced expression pattern of glutamate signaling genes associated with anhedonia.

Nikolay N Dygalo, Tatyana S Kalinina, Galina T Shishkina

Stress (Amsterdam, Netherlands) 2020 Nov

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Chronic stress can predispose vulnerable individuals to mood disorders, including depression. Glutamate, one of the key participants in this process, may exert both pathological and therapeutic psycho-emotional effects. However, the role of expression of genes encoding proteins that provide glutamatergic signal is still unclear. In this study, we attempted to distinguish changes in expression of glutamatergic genes associated with stress-induced anhedonia, a core symptom of depression, from those related to other stress-related effects. For this, expression of genes was compared between rats after a short-term stress, which did not yet cause depressive-like symptoms, and animals exposed chronically to different stressors that produce anhedonia-like responses. The changes in gene expression induced by chronic restraint or forced swimming concomitantly with anhedonia development demonstrated similar for both stressors patterns. Main features of the expression patterns include the decrease in mRNA levels for AMPA and NMDA subunits in the midbrain and hippocampus that is consistent with the hypothesis that "monoamine (serotonin)-Glutamate/GABA long neural circuit" involved in mood regulation. The decrease in expression of these subunits in the midbrain may attenuate glutamatergic drive on the serotonergic neurons promoting a shift of excitation/inhibition balance between glutamate and GABA in the forebrain regions resulting in anhedonia. In general, changes in expression of multiple genes involved in glutamatergic neurotransmission in the forebrain and brainstem regions suggest that stress-induced anhedonia may result from the network dysfunction of this neurotransmitter system.

Citation

Nikolay N Dygalo, Tatyana S Kalinina, Galina T Shishkina. Stress-induced expression pattern of glutamate signaling genes associated with anhedonia. Stress (Amsterdam, Netherlands). 2020 Nov;23(6):700-707