Abstract
Leptin targets the brain to regulate feeding, neuroendocrine function and metabolism. The leptin receptor is present in hypothalamic centers controlling energy metabolism as well as in the centrally projecting Edinger–Westphal nucleus (EWcp), a region implicated in the stress response and in various aspects of stress-related behaviors. We hypothesized that the stress response by cocaine- and amphetamine-regulated transcript (CART)-producing EWcp-neurons would depend on the animal’s energy state. To test this hypothesis, we investigated the effects of changes in energy state (mimicked by low, normal and high leptin levels, which were achieved by 24 h fasting, normal chow and leptin injection, respectively) on the response of CART neurons in the EWcp of rats subjected or not to acute restraint stress. Our data show that leptin treatment alone significantly increases CART mRNA expression in the rat EWcp and that in leptin receptor deficient (db/db) mice, the number of CART producing neurons in this nucleus is reduced. This suggests that leptin has a stimulatory effect on the production of CART in the EWcp under non-stressed condition. Under stressed condition, however, leptin blunts stress-induced activation of EWcp neurons and decreases their CART mRNA expression. Interestingly, fasting, does not influence the stress-induced activation of EWcp-neurons, and specifically EWcp-CART neurons are not activated. These results suggest that the stress response by the EWcp depends to some degree on the animal’s energy state, a mechanism that may contribute to a better understanding of the complex interplay between obesity and stress.
Highlights
In order to maintain homeostasis, vertebrates have to adapt to intrinsic or extrinsic stressors by a highly complicated process in which both neural and endocrine messengers from diverse sources are involved
We investigated the effects of changes in energy state on the response of cocaine- and amphetamine-regulated transcript (CART) neurons in the EWcp of rats subjected or not to acute restraint stress
Based on the expression of LepRb in the EWcp and the involvement of EWcp in stress response and energy balance, we hypothesized that EWcp neurons would respond to stress differentially under various energy states mimicked by low, normal and high plasma leptin levels
Summary
In order to maintain homeostasis, vertebrates have to adapt to intrinsic or extrinsic stressors by a highly complicated process in which both neural and endocrine messengers from diverse sources are involved. Depending on the type of stressor, specific stress-sensitive hypothalamic and extrahypothalamic brain centers interact with each other to eventually control the secretion of corticosteroids by the hypothalamic–pituitary–adrenal (HPA)axis (for references, see e.g., Chrousos and Gold, 1992). These hormones enable the organism to cope with the stress challenge (Sapolsky et al, 2000) but at the same time, urge it to spend a high amount of energy to this adaptation (Kozicz et al, 2011; Morava and Kozicz, 2013). We focus in particular on the roles of leptin and CART in the stress- and feeding-sensitive extrahypothalamic, centrally projecting Edinger–Westphal nucleus (EWcp)
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