Regulatory Changes in Neuroendocrine Stress-Integrative Circuitry Produced by a Variable Stress Paradigm

Abstract

Stress represents a complex stimulus to neuroendocrine systems regulating homeostasis. By and large, stress effects are mediated by stress-integrative corticotropin-releasing hormone (CRH) neurons present in the medial parvocellular division of the hypothalamic paraventricular nucleus (PVN). These neurons summate a large variety of neuronal and hormonal signals to eventually yield a physiologically meaningful level of circulating glucocorticoids. In the present experiments, we examined the effects of a chronic variable-stressor paradigm on indices of adrenocorticotropic hormone (ACTH) secretagogue biosynthesis in the PVN and adrenocorticosteroid receptor mRNA expression in the hippocampal formation, PVN and cortex. The variable-stressor paradigm produces a syndrome consistent with chronic stress, including baseline hypersecretion of corticosterone, ACTH and prolactin, and adrenal hypertrophy. CRH mRNA levels in the PVN are increased some 61 %, consistent with the observed hypothalamo-pituitary-adrenal (HPA) up-regulation. There was a small but significant increase in arginine vasopressin (AVP) mRNA expression in individual parvocellular PVN neurons (16%), and no demonstrable increase in the number of AVP mRNA-containing neurons. No change in AVP expression was seen in the magnocellular PVN, supraoptic or suprachiasmatic nuclei. In all, these data highlight the importance of CRH in maintaining HPA up-regulation in the face of prolonged challenge. To investigate effects of chronic stress on the regulation of glucocorticoid receptivity, mineralocorticoid receptor (MR) and glucocorticoid receptor mRNA expression was assessed in the hippocampus, frontoparietal cortex and PVN. Chronic stress significantly down-regulated MR mRNA expression in subfields CA1, CA3 and the dentate gyrus (DG), and GR mRNA expression in subfields CA1, the DG and frontoparietal cortex. The reduction in receptor biosynthesis suggests the capacity for stress to modulate the impact of glucocorticoid on hippocampal cell physiology at the genomic level, potentially influencing processes ranging from cognition to feedback regulation of the HPA axis. At the level of the parvocellular PVN, GR mRNA expression was decreased to 60% of control values. GR mRNA expression was negatively correlated with PVN CRH mRNA expression, suggesting a relationship between elevated CRH gene expression and down-regulation of GR at the level of the PVN.

Brief RU 38486 Treatment Normalizes the Effects of Chronic Stress on Calcium Currents in Rat Hippocampal CA1 Neurons

“…Indeed, our data clearly indicate that during the 21 days of unpredictable stress rats were exposed to elevated plasma corticosterone levels. Thus, in agreement with earlier studies (eg Herman et al, 1995;Alfarez et al, 2003), their gain in bodyweight was decreased and adrenal sizeFboth absolute and relative to body weightFwas increased. The absolute Ca-currents evoked in CA1 neurons from naïve rats by a voltage step to À20 mV are significantly increased 1-4 h after a brief (20 min) administration of corticosterone in vitro (cort; n ¼ 12 cells), compared to the vehicle treated group (veh; n ¼ 11; left panel).…”

“…Control rats were removed from their cages, handled briefly and weighed, for 21 days. The other rats were exposed for a 21-days period to (different) stressors twice daily in a random order (Chappell et al, 1986;Herman et al, 1995): (1) Immobilization: rats were placed in plastic immobilization cages for 1 h; (2) Cold immobilization: rats were placed in plastic immobilization cages in a cold room (41C) for 1 h; (3) Vibration: rats in group-cages were placed on top of an orbital shaker and shaken for 1 h at 30 rev/min; (4) Isolation: rats were moved to individual cages for a 24-h period; (5) Crowding: rats were housed four to six per cage for a 24-h period; (6) Swim: rats were placed in a plastic container filled with water (25-301C) for 30 min; (7) Coldwater swim: rats were placed in a plastic container filled with cold water (10-151C) for 5 min. Rats were exposed to cold only once per day.…”

Association between sleeping hours, working hours and obesity in Hong Kong Chinese: the ‘better health for better Hong Kong’ health promotion campaign

“…19,22,[26][27][28][29] In this regard, there is now growing epidemiological evidence suggesting the importance of psychosocial, cognitive and behavioral parameters and chronic diseases such as obesity, diabetes and cardiovascular diseases. [30][31][32] Although formal psychological testing were not performed in our subjects, it is conceivable that subjects who need to work long hours and have poor sleep may be under higher level of stress which might be reflected in their obesity.…”

Chronic stress enhances methamphetamine‐induced extracellular glutamate and excitotoxicity in the rat striatum

“…According to the CUS model, both type and time of stressor exposure vary. Therefore, this paradigm is not confounded with adaptation and produces higher baseline corticosterone levels compared to models of predictable stress (Araujo et al, 2003;Bielajew et al, 2002;Herman et al, 1995). Rats were exposed to stressors for 10 days (Matuszewich and Yamamoto, 2004).…”