Chronic social subordination stress modulates glutamic acid decarboxylase (GAD) 67 mRNA expression in central stress circuits

Abstract

Chronic social subordination is a well-known precipitant of numerous psychiatric and physiological health concerns. In this study, we examine the effects of chronic social stress in the visible burrow system (VBS) on the expression of glutamic acid decarboxylase (GAD) 67 and brain-derived neurotropic factor (BDNF) mRNA in forebrain stress circuitry. Male rats in the VBS system form a dominance hierarchy, whereby subordinate males exhibit neuroendocrine and physiological profiles characteristic of chronic exposure to stress. We found that social subordination decreases GAD67 mRNA in the peri-paraventricular nucleus region of the hypothalamus and the interfascicular nucleus of the bed nucleus of the stria terminalis (BNST), and increases in GAD67 mRNA in the hippocampus, medial prefrontal cortex, and dorsal medial hypothalamus. Expression of BDNF mRNA increased in the dorsal region of the BNST, but remained unchanged in all other regions examined. Results from this study indicate that social subordination is associated with several region-specific alterations in GAD67 mRNA expression in central stress circuits, whereas changes in the expression of BDNF mRNA are limited to the BNST.

Variable Effects of Acoustic Trauma on Behavioral and Neural Correlates of Tinnitus In Individual Animals

“…Animals housed alone show much higher stress levels than animals housed in pairs or groups (Sharp et al, 2003). However, dominance struggles between pairs can cause a great deal of stress to the subordinate animal (Makinson et al, 2015). Any or all of these stressing factors could lead to a potential difference in the outcome of sound exposure, especially since it is known that sound exposure itself leads to increased levels of stress hormones (Kozlovsky et al, 2009).…”

Maternal immune activation alters glutamic acid decarboxylase-67 expression in the brains of adult rat offspring

“…Semi-adjacent sections were processed for the in situ hybridization localization of GAD 67 mRNA using a 35 S-labeled cDNA probe, as previously described (Seroogy and Herman, 1997; Hemmerle et al, 2012, 2015; Makinson et al, 2015). Briefly, slides were pretreated, dehydrated and delipidated prior to hybridization.…”

The visible burrow system: A view from across the hall

“…However, it is important to note that reduced 5HT1A binding was not observed in the NRS group [15], differentiating this group from both DOM and SRS animals and implying intact serotonergic inhibition of hippocampal output neurons. Elevated expression of glutamic acid decarboxylase 67 (GAD67) mRNA is observed in all hippocampal subfields, as well as the medial prefrontal cortex of SUB animals [26]. GAD67 is an enzyme responsible for conversion of glutamate to GABA in neurons, and contributes to generation of a readily releasable (rather than stored) pool of GABA at terminals [27].…”

“…In general, changes restricted to DOMs are more minor in extent, limited to decreased GAD67 expression in PVN projecting neurons of the peri-PVN zone and intrafasicular BST [26] and enhanced expression of orexin receptors in the prefrontal cortex [45]. However, while the weight of evidence supports a wide-reaching alteration in brain stress circuits, it is important to consider the limitations of these data.…”

“…Common features to both VBS and CVS include up-regulation of GAD67 mRNA expression in hippocampus and prefrontal cortex [26, 47]. This implies that both stressors may promote inhibition of stress regulatory structures, which may participate in upstream control of glucocorticoid negative feedback.…”