Role of orexin neurons as mediators of the central effects induced by growth hormone

Abstract

Orexins, also known as hypocretin, neuropeptides are responsible for regulating arousal, wakefulness, appetite, blood sugar control, and other physiological processes. They are found in neurons of the lateral hypothalamus and have neuroexcitatory effects. The lack of orexin in the brain is associated with narcolepsy in humans and animals, thus indicating its importance in the sleep-wake control. Interestingly, the growth hormone (GH) also modulates various biological functions controlled by orexins neurons. For example, GH-deficient individuals have severe metabolic disorders, such as sleep disturbance, hyperphagia, changes in glycemic control, obesity, among others. They feature changes in attention, wakefulness and sleep. However, a possible interaction between GH and orexin has never been directly studied. Thus, in this project, we formulated a hypothesis that GH may act directly on the orexin neurons, supporting neuroanatomical for many of the dysfunctions presented in GH deficiency, mediating the change in the functioning of orexin neurons. To investigate a possible interrelationship between GH and orexin neurons, we use mice that have GH receptor deficiency only in orexin neurons (GHR flox / flox orexin Cre). In this way, we can study the effects of GH exclusively on these neurons without affecting other cell populations with the GH receptor. The evolution of the weight of these animals will be monitored until adulthood, when they will be housed in individual boxes and tested for metabolic assessment, glucose and food intake. Subgroups will be subjected to food restriction and exercise along with its controls to study physiological situations in which GH secretion is high. From these experiments, we hope to better understand the mechanics involved in the communication between growth hormone and orexins neurons. Our data has the potential to identify the specific neuronal circuit involved in many of the effects of GH. (AU)