Chronic stress dampens excitatory synaptic gain in the paraventricular nucleus of the hypothalamus

Diabetes mellitus (DM), as chronic stress activates the hypothalamo-pituitary-adrenocortical axis. We examined whether arginine vasopressin (AVP) and the hypothalamic paraventricular nucleus (PVN) participate in DM-induced chronic stress symptoms. AVP-deficient Brattleboro or PVN-lesioned Wistar rats were used with heterozygous or sham-operated controls. The rats were studied 2 wk after a single injection of streptozotocin. The appearance of DM (enhanced water consumption and blood glucose elevation) and the chronic stress-like somatic changes (body weight decrease, thymus involution, adrenal gland hypertrophy) were not influenced by the lack of AVP. By contrast, PVN lesion significantly attenuated DM-induced thymus involution and adrenal gland hypertrophy as well as the increase in water consumption. The corticotropin-releasing hormone mRNA in PVN was diminished by DM and elevated by the lack of AVP without interaction. DM elevated the proopiomelanocortin (POMC) mRNA in the anterior lobe of the pituitary. The lack of AVP had no effect, whereas lesioning the PVN significantly diminished the elevation. The elevated basal corticosterone plasma levels detectable in DM were influenced neither by the lack of AVP nor by lesioning the PVN. Thus the lack of AVP had no influence on DM-induced chronic stress symptoms, but lesioning the PVN attenuated part of them. However, the lack of elevation in POMC mRNA after PVN lesion, together with the maintained corticosterone elevation, suggests that direct adrenal gland activation occurs in untreated DM.

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Chronic Stress Induces Persistent Hypertension and Increases NMDA Receptor Activity in the Paraventricular Nucleus in Borderline Hypertensive Rats

The FASEB Journal ◽

10.1096/fasebj.2020.34.s1.03968 ◽

2020 ◽

Vol 34 (S1) ◽

pp. 1-1

Author(s):

Jing-Jing Zhou ◽

Jian-ying Shao ◽

Shao-Rui Chen ◽

De-Pei Li ◽

Hui-Lin Pan

Keyword(s):

Nmda Receptor ◽

Chronic Stress ◽

Paraventricular Nucleus ◽

Receptor Activity ◽

Hypertensive Rats

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The Anteroventral Bed Nucleus of the Stria Terminalis Differentially Regulates Hypothalamic-Pituitary-Adrenocortical Axis Responses to Acute and Chronic Stress

Endocrinology ◽

10.1210/en.2007-0883 ◽

2007 ◽

Vol 149 (2) ◽

pp. 818-826 ◽

Cited By ~ 70

Author(s):

Dennis C. Choi ◽

Nathan K. Evanson ◽

Amy R. Furay ◽

Yvonne M. Ulrich-Lai ◽

Michelle M. Ostrander ◽

...

Keyword(s):

Chronic Stress ◽

Hpa Axis ◽

Paraventricular Nucleus ◽

Restraint Stress ◽

Body Weight Gain ◽

Stria Terminalis ◽

Thymic Involution ◽

Bed Nucleus ◽

Acute And Chronic Stress

The anteroventral region of the bed nucleus of the stria terminalis (BST) stimulates hypothalamic-pituitary-adrenocortical (HPA) axis responses to acute stress. However, the role of the anterior BST nuclei in chronic drive of the HPA axis has yet to be established. Therefore, this study tests the role of the anteroventral BST in physiological responses to chronic drive, using a chronic variable stress (CVS) model. Male Sprague-Dawley rats received either bilateral ibotenate lesions, targeting the anteroventral BST, or vehicle injection into the same region. Half of the lesion and control rats were exposed to a 14-d CVS paradigm consisting of twice-daily exposure to unpredictable, alternating stressors. The remaining rats were nonhandled control animals that remained in home cages. On the morning after the end of CVS exposure, all rats were exposed to a novel restraint stress challenge. CVS induced attenuated body weight gain, adrenal hypertrophy, thymic involution, and enhanced CRH mRNA in hypophysiotrophic neurons of the hypothalamic paraventricular nucleus, none of which were affected by anteroventral BST lesions. In the absence of CVS, lesions attenuated the plasma corticosterone and paraventricular nucleus c-fos mRNA responses to the acute restraint stress. In contrast, lesions of the anteroventral BST elevated plasma ACTH and corticosterone responses to novel restraint in the rats previously exposed to CVS. These data suggest that the anterior BST plays very different roles in integrating acute stimulation and chronic drive of the HPA axis, perhaps mediated by chronic stress-induced recruitment of distinct BST cell groups or functional reorganization of stress-integrative circuits.

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Adaptive synaptic plasticity maintains CRH neuron output during chronic glucocorticoid exposure

10.1101/2020.04.27.064725 ◽

2020 ◽

Author(s):

Neilen Rasiah ◽

David Rosenegger ◽

Nuria Daviu ◽

Tamás Füzesi ◽

Jessie Muir ◽

...

Keyword(s):

Synaptic Plasticity ◽

Chronic Stress ◽

Paraventricular Nucleus ◽

Intrinsic Excitability ◽

Intrinsic Activity ◽

Endocrine Response ◽

Synaptic Scaling ◽

Response To Stress ◽

Surprising Discovery

AbstractAn increase in circulating glucocorticoids (CORT) is an essential part of the response to stress. Sustained elevations of CORT, however, have dramatic consequences on behavior, endocrine systems and peripheral organs. Critically, they dampen the endocrine response to acute challenges and decrease intrinsic excitability of corticotropin-releasing hormone neurons in the paraventricular nucleus (CRHPVN), suggesting key circuits may be less responsive to stress. Here, we make the surprising discovery that CRHPVN neurons harness a form of adaptive synaptic scaling to escape the persistent negative feedback pressure from CORT and maintain stable output in vivo. Specifically, there is an increase in glutamatergic drive to these cells that is mediated by a postsynaptic, multiplicative increase in synaptic strength. These findings suggest that dysfunctions associated with chronic stress may not be due to the primary actions of CORT, but instead reflect the emergence of synaptic adaptations as networks seek to re-establish intrinsic activity setpoints.

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