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17 - hypothalmic Orexin neurons regulate arousal, Yamanak, A

17 - hypothalmic Orexin neurons regulate arousal, Yamanak,...

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Article 14:Hypo Orexin Neurons Regulate Arousal According to Energy Balance in Mice Summary -mammals respond to reduced food availability becoming more wakeful and active -hypothalamic orexin neurons monitor indicators of energy balance and mediate adaptive augmentation of arousal in response to fasting -activity of isolated orexin neurons is inhibited by glucose and leptin stimulated by ghrelin Introduction -motivated behaviors such as food seeking are critically dependent upon arousal pathway -when faced with negative energy balance due to reduced food availability, mammals respond with phases of increased wakefulness and locomoteor activity that support food seeking -orexins/hypocretins are a pair of neuropeptides expressed by neurons in lateral hypothalamic area (LHA) of brain implicated in brain arousal and motivated behaviour -arexin A and orexin B are derived from common precursor peptide of the prepro-orexin gene - actions of orexins are mediated by G-protein-coupled receptors: orexin receptor type 1 and type 2 - orexinergic system is placed well to influence the arousal, motivational, metabolic, autonomic, and motor processes necessary to elicit homeostatically appropriate behaviours -orexins are administered centrally to rodents reported to elevate sympathetic tone, plasma corticosone levels, metabolic rate and food intake and locomotor activity and wakefulness -observed in fasted animals - antagonism of orexin receptor type 1 causes reduced food intake and weight loss in rodents - mice lacking either orexin gene, orexin neurons, mutations in orexin type 2 receptor have symptoms similar to narcolepsy - human narcolepsy is associated with specific destruction of orexin neurons -orexin receptor type 1 is associated with reduced food intake and weight reduction in rodents -observations are consistent with hypothesis that orexins provide link between metabolic and motivated behavior
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