Mineralocorticoid Receptor Overexpression in Basolateral Amygdala Reduces Corticosterone Secretion and Anxiety

Global cerebral ischemia (GCI) in rats has been shown to promote exploration of anxiogenic zones of the Elevated-Plus Maze (EPM) and Open Field Test (OFT). This study investigated changes in impulsive choice and/or defensive responses as possible contributors of heightened anxiogenic exploration observed after ischemia. Impulsivity was assessed using delay discounting (DD) paradigms, while the Predator Odour Test (PO) served to assess changes in defensive responses towards a naturally aversive stimulus. Male Long Evans rats underwent 9 days of autoshaping training and 24 days of DD training prior to GCI or sham surgery (n = 9/group). Post-surgery, rats completed the OFT, EPM, and PO, followed by 6 days of DD sessions. Blood droplets served to evaluate corticosterone secretion associated with PO exposure. With impulsivity being regulated through mesocorticolimbic monoaminergic pathways, we also characterised post-ischemic changes in the expression of dopamine D2 receptors (DRD2), dopamine transporters (DAT), and 1FosB in the basolateral amygdala (BLA), nucleus accumbens core (NAcC) and shell (NAcS), and ventromedial prefrontal cortex (vmPFC) using immunohistofluorescence. Our findings revealed no impact of GCI on delay discounting rates, while PO approach behaviours were minimally affected. Nonetheless, GCI significantly reduced DRD2 and ΔFosB-ir in the NAcS and NAcC, respectively, while DAT-ir was diminished in both NAc subregions. Collectively, our findings refine the understanding of cognitive-behavioural and biochemical responses following stroke or cardiac arrest. They support significant alterations to the dopaminergic mesocorticolimbic pathway after ischemia, which are not associated with altered impulsive choice in a DD task but may influence locomotor exploration of the OFT and EPM.

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Toxoplasma gondii infection induces dendritic retraction in basolateral amygdala accompanied by reduced corticosterone secretion

Disease Models & Mechanisms ◽

10.1242/dmm.009928 ◽

2012 ◽

Vol 6 (2) ◽

pp. 516-520 ◽

Cited By ~ 41

Author(s):

R. Mitra ◽

R. M. Sapolsky ◽

A. Vyas

Keyword(s):

Toxoplasma Gondii ◽

Basolateral Amygdala ◽

Corticosterone Secretion ◽

Toxoplasma Gondii Infection

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Morpholino-mediated knockdown of the brain mineralocorticoid receptor affects glucocorticoid signaling and neuroplasticity in wild ocellated wrasse (Symphodus ocellatus)

10.1101/2021.11.17.468986 ◽

2021 ◽

Author(s):

Bridget M. Nugent ◽

Kelly A. Stiver ◽

Jiawei Han ◽

Holly K Kindsvater ◽

Susan E. Marsh-Rollo ◽

...

Keyword(s):

Phenotypic Variation ◽

Mineralocorticoid Receptor ◽

Basolateral Amygdala ◽

Experimental Manipulation ◽

Genomic Variation ◽

Stress Axis ◽

Male Behavior ◽

Reproductive Tactics ◽

Glucocorticoid Signaling ◽

The Brain

Uncovering the genetic, physiological, and developmental mechanisms underlying phenotypic variation is necessary for understanding how genetic and genomic variation shape phenotypic variation and for discovering possible targets of selection. Although the neural and endocrine mechanisms underlying social behavior are evolutionarily ancient, we lack an understanding of the proximate causes and evolutionary consequences of variation in these mechanisms. Here, we examine in the natural environment the behavioral, neuromolecular, and fitness consequences of a morpholino-mediated knockdown of the mineralocorticoid receptor (MR) in the brain of nesting males of the ocellated wrasse, Symphodus ocellatus, a species with male alternative reproductive tactics. Even though MR knockdown did not significantly change male behavior directly, this experimental manipulation strongly altered glucocorticoid signaling and neuroplasticity in the preoptic area, the putative hippocampus homolog, and the putative basolateral amygdala homolog. We also found that individual variation in stress axis gene expression and neuroplasticity is strongly associated with variation in male behavior and fitness-related traits. The brain region-specific effects of MR knockdown on phenotypic integration in the wild reported here suggest specific neuroendocrine and neuroplasticity pathways that may be targets of selection.

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SK2 potassium channel overexpression in basolateral amygdala reduces anxiety, stress-induced corticosterone secretion and dendritic arborization

Molecular Psychiatry ◽

10.1038/mp.2009.9 ◽

2009 ◽

Vol 14 (9) ◽

pp. 847-855 ◽

Cited By ~ 41

Author(s):

R Mitra ◽

D Ferguson ◽

R M Sapolsky

Keyword(s):

Potassium Channel ◽

Basolateral Amygdala ◽

Dendritic Arborization ◽

Corticosterone Secretion

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Regulation of aldosterone secretion by mineralocorticoid receptor–mediated signaling

Journal of Endocrinology ◽

10.1530/joe-16-0452 ◽

2017 ◽

Vol 232 (3) ◽

pp. 525-534 ◽

Cited By ~ 16

Author(s):

Cherish Chong ◽

Anis Hamid ◽

Tham Yao ◽

Amanda E Garza ◽

Luminita H Pojoga ◽

...

Keyword(s):

Mineralocorticoid Receptor ◽

Ex Vivo ◽

Zona Glomerulosa ◽

Zona Fasciculata ◽

Aldosterone Secretion ◽

Aldosterone Synthase ◽

Adrenal Steroidogenesis ◽

Corticosterone Secretion ◽

Aldosterone Production ◽

Male Wistar Rats

We posit the existence of a paracrine/autocrine negative feedback loop, mediated by the mineralocorticoid receptor (MR), regulating aldosterone secretion. To assess this hypothesis, we asked whether altering MR activity in zona glomerulosa (ZG) cells affects aldosterone production. To this end, we studied ex vivo ZG cells isolated from male Wistar rats fed chow containing either high (1.6% Na+ (HS)) or low (0.03% Na+ (LS)) amount of sodium. Western blot analyses demonstrated that MR was present in both the ZG and zona fasciculata/zona reticularis (ZF/ZR/ZR). In ZG cells isolated from rats on LS chow, MR activation by fludrocortisone produced a 20% and 60% reduction in aldosterone secretion basally and in response to angiotensin II (ANGII) stimulation, respectively. Corticosterone secretion was increased in these cells suggesting that aldosterone synthase activity was being reduced by fludrocortisone. In contrast, canrenoic acid, an MR antagonist, enhanced aldosterone production by up to 30% both basally and in response to ANGII. Similar responses were observed in ZG cells from rats fed HS. Modulating glucocorticoid receptor (GR) activity did not alter aldosterone production by ZG cells; however, altering GR activity did modify corticosterone production from ZF/ZR/ZR cells both basally and in response to adrenocorticotropic hormone (ACTH). Additionally, activating the MR in ZF/ZR/ZR cells strikingly reduced corticosterone secretion. In summary, these data support the hypothesis that negative ultra-short feedback loops regulate adrenal steroidogenesis. In the ZG, aldosterone secretion is regulated by the MR, but not the GR, an effect that appears to be secondary to a change in aldosterone synthase activity.

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The Role of the Forebrain Glucocorticoid Receptor in Acute and Chronic Stress

Endocrinology ◽

10.1210/en.2008-0642 ◽

2008 ◽

Vol 149 (11) ◽

pp. 5482-5490 ◽

Cited By ~ 107

Author(s):

Amy R. Furay ◽

Amy E. Bruestle ◽

James P. Herman

Keyword(s):

Glucocorticoid Receptor ◽

Chronic Stress ◽

Hpa Axis ◽

Negative Feedback ◽

Basolateral Amygdala ◽

Feedback Regulation ◽

Negative Feedback Regulation ◽

Acute And Chronic Stress ◽

Corticosterone Secretion

Previous work has implicated the forebrain glucocorticoid receptor (GR) in feedback regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis. The present series of experiments used male mice with a targeted forebrain-specific GR knockout (in which forebrain includes the prefrontal cortex, hippocampus, and basolateral amygdala) to determine the role of forebrain GR in HPA axis regulation after stress. The data indicate that the forebrain GR is necessary for maintaining basal regulation of corticosterone secretion in the morning, confirming its role in HPA axis regulation. Our data further indicate that the forebrain GR is necessary for negative feedback after both mild and robust acute psychogenic stressors but not hypoxia, a systemic stressor. In contrast, forebrain-specific GR knockout and control mice exhibit equivalent HPA axis hyperactivity and facilitation after chronic variable stress, suggesting that changes in forebrain GR are not essential for chronic stress-induced pathology. These studies provide novel and definitive evidence that the forebrain GR selectively contributes negative feedback regulation of HPA axis responses to psychogenic stressors. Moreover, the data indicate that chronic stress-induced alterations in HPA axis function are mediated by mechanisms independent of the forebrain GR. Overall, the data are consistent with an essential role of the forebrain GR in coordinating endocrine responses to stimuli of a psychological origin.

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