Abstract
Correlations amongst the rat glutamatergic system, glia, and depression, as well as the underlying mechanism of astrocyte impairment, as a trigger of depression, were investigated. Rats were submitted to different durations of chronic unpredictable mild stress to induce depressive-like behavior and evaluated by weight change, sucrose preference test, open field test, and novelty suppressed feeding test. High-performance liquid chromatography was employed to detect glutamate content of hippocampal protein expression during Western blot and immunofluorescence. Results showed that 21-day chronic unpredictable mild stress was sufficient for inducing significant depressive-like behavior (reduced body weight and sucrose preference, increased feeding, and immobility time) in a model of depression. Chronic unpredictable mild stress increased the level of hippocampal glutamate, while intervention caused a considerable rise in the expression levels of Bax, caspase 3, and calcium/calmodulin-dependent protein kinase II, accompanied by a down-regulated level of B-cell lymphoma-2. Exposure to this stress model reduced hippocampal glutamate ionotropic receptor N-methyl-D-aspartic acid type subunit 2A, neuronal nuclear protein, and glial fibrillary acidic protein expression levels while it raised the level of ionotropic glutamate receptor N-methyl-D-aspartic acid type subunit 2B level. It is concluded that chronic stress induces excessive glutamate release and overstimulation of N-methyl-D-aspartic acid receptors, followed by astrocytic apoptosis. Also, in depression, calcium overload in astrocytes is attributed to an underlying mechanism of astrocyte impairment.
Highlights
Accumulating studies reveal that the glutamatergic system is implicated in the etiopathology and treatment of depression (Deutschenbaur et al, 2016)
There was no significant difference between Day 1 and 7 in the 7-day chronic unpredictable mild stress (CUMS) group, 14-day CUMS group, and 28-day CUMS group, but a significant reduction was found on Day 14 for the 14day CUMS group (P < 0.001; Fig. 1B) and on Day 14 (P = 0.021; Fig. 1B), 21 (P = 0.016; Fig. 1B) and 28 (P = 0.002; Fig. 1B) for the 28-day CUMS group, when compared with the sucrose consumption rate on Day 1 for the same group
A CUMS rat model was employed to investigate the interrelationships between the glutamate system, glia, and depression, further, to probe into the underlying mechanism of astrocyte impairment in depression
Summary
Accumulating studies reveal that the glutamatergic system is implicated in the etiopathology and treatment of depression (Deutschenbaur et al, 2016). Glutamate levels are affected in the plasma (Mauri et al, 1998), cerebrospinal fluid (Frye et al, 2007), and the depressed brain (Hasler et al, 2007; Sanacora et al, 2008) and revealed by magnetic resonance spectroscopy (Yildiz-Yesiloglu et al, 2006) and post-mortem studies (Hashimoto et al, 2007), supporting a relation between glutamate and depression. The function of glial cell reuse of glutamate via the glutamate/glutamine cycle (Lebon et al, 2002) is related to the primary etiology of mood disorders (Kugaya and Sanacora, 2005). A reduction in glial cell number and density is reported by several post-mortem reports (Cotter et al, 2001; Ongur et al, 1998; Rajkowska et al, 1999)
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