Neuroscience
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Cholecystokinin (CCK) released from the small intestine increases the activity of vagal afferents that relay satiety signals to the caudal nucleus of the solitary tract (cNTS). A caudal subset of A2 noradrenergic neurons within the cNTS that express prolactin-releasing peptide (PrRP) have been proposed to mediate CCK-induced satiety. However, the ability of exogenous CCK to activate cFos expression by PrRP neurons has only been reported in rats and mice after a very high dose (i.e., 50 μg/kg BW) that also activates the hypothalamic-pituitary-adrenal stress axis. ⋯ CCK-treated rats displayed increased numbers of cFos-positive cNTS neurons compared to non-injected and saline-injected controls, with no effect of diet. In chow-fed rats, a significantly larger proportion of PrRP neurons were activated after CCK treatment compared to controls; conversely, CCK did not increase PrRP neuronal activation in HFD-fed rats. Collectively, these results indicate that a relatively low dose of exogenous CCK is sufficient to activate PrRP neurons in chow-fed rats, and that this effect is blunted in rats maintained for several weeks on HFD.
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Social interaction is important for survival in most social species including humans. To ensure social activities, individuals experience reward from social interaction, generating a powerfully reinforcing process. Here we hypothesized that reward from social interaction in a juvenile male rat pair may be enhanced by ghrelin, a circulating hormone that has been shown to enhance reward from other natural (e.g. food, sex) as well as artificial reinforcers (e.g. alcohol and other drugs of abuse). ⋯ We found that ghrelin increased and a ghrelin antagonist decreased preference for social interaction, but only in the heavier partner in a social pair. In addition, we found that administered ghrelin induced a positive association between preference for social interaction and body weight difference within socially interacting pairs, where larger ghrelin treated rats preferred social interaction, whereas smaller ghrelin treated rats avoided it, which raises the question if ghrelin could have a role in implementing social hierarchies in rats. In summary, we conclude that ghrelin signaling increases the reward from social interaction in a manner that reflects the degree of divergence in body weight between the social pair.
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The aim of this study was to indentify the involvement of leptin receptors (LepR) in astrocytes in hippocampal synaptic transmission and plasticity and metabolism. To this end we used a genetic mouse model (GFAP-LepR-/-) of specific LepR ablation in GFAP positive cells and recorded excitatory postsynaptic potentials (fEPSPs) within the CA1 area. Glutamate (Glu) uptake and the expression of Glu transporters (EEAT3, GLT-1 and GLAST) and enzymes involved in Glu metabolism (glutamine synthase, GABA decarboxylase 65 and 67) were quantified. ⋯ Hippocampal slices from GFAP-LepR-/- mice displayed lower Glu uptake efficacy together with up-regulation of GLT-1, glutamine synthase, GFAP and GLUT-1. In conclusion, astrocyte LepRs are involved in the maintenance of Glu homeostasis and Glu neurotransmission within the hippocampus. Our findings support a role of hippocampal LepRs in synaptic plasticity, which could have an impact on memory and learning processes.
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Review
Immunometabolic Changes in Glia - A Potential Role in the Pathophysiology of Obesity and Diabetes.
Chronic low-grade inflammation is a feature of the pathophysiology of obesity and diabetes in the CNS as well as peripheral tissues. Glial cells are critical mediators of the response to inflammation in the brain. Key features of glia include their metabolic flexibility, sensitivity to changes in the CNS microenvironment, and ability to rapidly adapt their function accordingly. ⋯ Inflammation is an energetically expensive process that requires adaptive changes in cellular metabolism and, in turn, metabolic intermediates can also have immunomodulatory actions. Such "immunometabolic" changes in peripheral immune cells have been implicated in contributing to disease pathology in obesity and diabetes. This review will discuss the evidence for a role of immunometabolic changes in glial cells in the systemic regulation of energy and glucose homeostasis, and how this changes in the context of obesity and diabetes.