•Stress exposure affects the regulation of brain IL-1 in male but not female rats.•Glucocorticoids suppress norepinephrine turnover in male but not female rats.•Metyrapone increases brain IL-1 more ...prominently in male compared to female rats.•Propranolol blocks the increase in brain IL-1 observed following metyrapone treatment.
Elevations in brain interleukin-1 beta (IL-1β) during chronic stress exposure have been implicated in behavioral and cognitive impairments associated with depression and anxiety. Two critical regulators of brain IL-1β production during times of stress are glucocorticoids and catecholamines. These hormones work in opposition to one another to inhibit (via glucocorticoid receptors) or stimulate (via beta-adrenergic receptors: β-AR) IL-1β production. While chronic stress often heightens both corticosterone and catecholamine levels, it remains unknown as to how chronic stress may affect the “yin-yang” balance between adrenergic stimulation and glucocorticoid suppression of brain IL-1β. To investigate this further, male and female rats underwent 4 days of stress exposure or served as non-stressed controls. On day 5, animals were administered propranolol (β-AR antagonist), metyrapone (a glucocorticoid synthesis inhibitor), vehicle, or both drugs and brain IL-1β mRNA was measured by rtPCR in limbic brain areas. In males, administration of propranolol had no effect on IL-1β expression in non-stressed controls but significantly reduced IL-1β in the hippocampus and amygdala of chronically stressed animals. In females, propranolol significantly reduced IL-1β in the amygdala and hypothalamus of both control and stressed rats. In male rats, metyrapone treatment significantly increased IL-1β mRNA regardless of stress treatment in all brain areas, while in female rats metyrapone only increased IL-1β in the hypothalamus. Interestingly, propranolol treatment blocked the metyrapone-induced increase in brain IL-1β indicating the increase in brain IL-1β following metyrapone treatment was due to increase β-AR activation. Additional studies revealed that metyrapone significantly increases norepinephrine turnover in the hypothalamus and medial prefrontal cortex in male rats and that microglia appear to be the cell type contributing to the production of IL-1β. Overall, data reveal that stress exposure in male rats affects the regulation of brain IL-1β by the norepinephrine-β-AR pathway, while stress had no effect in the regulation of brain IL-1β in female rats.
Abstract The physiological and behavioral effects of stress are well characterized. Endocannabinoids are produced on demand and function to attenuate many of the physiological effects of the stress ...response. The endocannabinoid system is made up of cannabinoid receptors, the fatty acid signaling molecules that bind to and activate these receptors, and the enzymes that synthesize and catabolize these endocannabinoid signaling molecules. Cannabinoid research has recently grown substantially, due in no small part to the development of genetic research models as well as highly selective pharmaceutical tools. The purpose of this minireview is to discuss a subset of the many parallels between cannabinoid and behavioral neuroimmunology research, with specific discussion of interactions between the endocannabinoid system and psychological stress, emotionality, and inflammation.
Abstract Induction of brain cytokines during times of stress has potent effects on altering behavior, mood, and cognitive functioning. Currently, it is unknown why exposure to some stressors such as ...tailshock and footshock elevate brain cytokines, while exposure to swim, predator odor, and restraint stress do not. Recent data indicate that brain noradrenergic signaling mediates brain cytokine production suggests magnitude of norepinephrine release during stress may be critical in initiating brain cytokine production. The aim of the current study was to investigate stress-induced brain cytokines between rat strains that differ in their magnitude of stress responsiveness as measured by brain norepinephrine and HPA responses. Sprague-Dawley and Fischer rats were placed in a restraint bag for 1 h or 2 h and sacrificed immediately following stressor termination. Exposure to restraint significantly elevated hypothalamic interleukin (IL)-1β and IL-1 receptor type (R) 2 mRNA after 1 h and IL-1β protein after 2 h in the high stress responsive Fischer rats, but not in Sprague-Dawley rats. IL-6, IL-1R1, Il-1 receptor antagonist (RA), and cyclooxygenase (Cox)-2 mRNA were not altered and neither there was expression of any cytokines in the hippocampus or circulating cytokines in either strain. Administration of desipramine (a norepinephrine reuptake inhibitor) to Sprague-Dawley rats was sufficient either alone or in combination with stress to increase IL-1β mRNA in the hypothalamus and desipramine combined with stress was sufficient to increase IL-1R2 mRNA in the hypothalamus. These data support our hypothesis that there is a critical threshold of brain norepinephrine necessary to stimulate brain cytokines, which may help to explain why severe stressors are more commonly reported to induce brain cytokines. These data also suggest an organisms' susceptibility to stress-induced brain cytokine production, depends on responsiveness and regulation of noradrenergic neurons.
Colorado's adult obesity rate has more than doubled since 1995, prompting its Department of Public Health and Environment to list obesity as its top prevention priority. To initiate comprehensive and ...effective action, the department used a well-known evidence-based public health framework developed by Brownson and others. This article describes the tools and process developed to conduct 2 of the 7 stages in this framework that challenge public health organizations: reviewing the literature and prioritizing effective strategies from that literature. Forty-five department staff participated in an intensive literature review training to identify physical activity and nutrition strategies that effectively address obesity and worked with external stakeholders to prioritize strategies for the state. Divided into 8 multidisciplinary teams organized by the setting where public health could exert leverage, they scanned the scientific literature to identify potential strategies to implement. These teams were trained to use standardized tools to critique findings, systematically abstract key information, and classify the evidence level for each of 58 identified strategies. Next, departmental subject matter experts and representatives from local public health and nonprofit health agencies selected and applied prioritization criteria to rank the 58 strategies. A team charter, group facilitation tools, and 2 web-based surveys were used in the prioritization stage. This process offered the staff a shared experience to gain hands-on practice completing literature reviews and selecting evidence-based strategies, thereby enhancing Colorado's obesity prevention efforts and improving public health capacity. Practitioners can use these tools and methodology to replicate this process for other health priorities.
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