Effects of Acute Stress or Centrally Injected Interleukin-1beta on Neuropeptide Expression in the Immune System

Acute stress stimulates the expression and release of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) from the hypothalamus, and the pro-opiomelanocortin products beta-endorphin and ACTH from the anterior pituitary. These neuropeptides are also expressed in immune tissues, and it has been proposed that they may modulate immune responses to stress through paracrine mechanisms. We subjected rats to restraint stress or central injection of interleukin (IL)-1beta to determine whether these acute stimuli can alter the expression of neuropeptides in the spleen and thymus. Restraint stress significantly increased the contents of all these neuropeptides in thymic, but not splenic, extracts. A single icv injection of IL-1beta increased contents of CRH, AVP, ACTH and beta-endorphin in the spleens of both sham-operated and adrenalectomised (ADX) rats. IL-1beta increased thymic contents of CRH and ACTH in sham-operated rats but these increases were not observed in ADX rats. These results suggest that the effects of IL-1beta on neuropeptide expression in the spleen are independent of glucocorticoids, whereas IL-1beta stimulation of neuropeptide expression in the thymus is dependent on circulating glucocorticoids. There were significant correlations between increases in CRH, ACTH and beta-endorphin in the spleen, and between CRH and ACTH in the thymus, consistent with the suggestion that IL-1beta-induced increases in ACTH and beta-endorphin may be mediated through CRH. These results provide evidence that stressors can directly influence neuropeptide expression in immune tissues. Thus stress may influence immune functions through paracrine mechanisms involving locally synthesised neuropeptides as well as through activation of the hypothalamo-pituitary-adrenal axis.     

Hypothalamo-Pituitary-Adrenocortical Regulation Following Lesions of the Central Nucleus of the Amygdala

Previous reports indicate that the central nucleus of the amygdala (CeA) stimulates adrenocorticotropin and corticosterone secretion, suggesting a role for this region in central hypothalamo-pituitary-adrenocortical (HPA) stress regulation. To evaluate this hypothesis, this study assessed the impact of CeA lesion on the response of hypophysiotrophic paraventricular nucleus (PVN) neurons to acute restraint and chronic unpredictable stress exposure. In contrast to previous reports, CeA lesions did not affect corticosterone or ACTH secretion induced by acute stress. Acute restraint increased PVN corticotropin releasing hormone (CRH) mRNA expression, increased the number of parvocellular PVN neurons expressing the co-secretagogue arginine vasopressin (AVP), and induced cFOS mRNA expression in the parvocellular PVN. However, there was no additional effect of CeA lesion on any measure of PVN activation. Chronic unpredictable stress exposure induced long-term activation of the HPA axis, noted by thymic involution, adrenal hypertrophy and increased PVN CRH mRNA expression. Stress-induced changes in thymus and adrenal weights were not affected by CeA lesion. Further, CeA lesion rats did not differ from controls in post-stress CRH mRNA expression. However, basal CRH mRNA expression was increased in the PVN of CeA rats, suggesting that the CeA plays a role in long-term inhibition of the PVN. The results of these studies are not consistent with the hypothesis that the CeA is necessary for stress-induced pituitary-adrenocortical activation. Rather, this region may play a stressor-specific modulatory role in regulation of HPA function.     

The Origins of Hopelessness Among Inner-City African-American Adolescents

Much has been written in recent years about hopelessness among residents of impoverished inner-city neighborhoods, but little research has been conducted on the origins of hopelessness. The literature on social disorganization and the literature on child development independently suggest two possible causes of hopelessness among adolescents: disruptive events and lack of connectedness to people and institutions. We explore these two factors as predictors of hopelessness for 5895 youths living in impoverished inner-city neighborhoods in Mobile, Alabama. The longitudinal data for this study allow us to explore the development of hopelessness over time, predicted by prior levels of disruption and connectedness. The results show that over time several variables associated with disruption (Change in Mother Figure, Exposure to Violence, Traumatic Stress, Worry) and connectedness (Sense of Community, Warmth Toward Mother, Religiosity) are positively or negatively associated with increased feelings of hopelessness among inner-city adolescents.