Neuroendocrinology

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Dr. Belsham studies how an intricate system of neurons in the brain controls many of our basic physiological functions, such as feeding, reproduction, and our day-night cycles. These neurons contain specific neuropeptides that distinguish their roles and she has immortalized these neurons to generate "neurons in a dish", which are used globally to study how individual brain cells operate. Her team has discovered that neurons respond to signals with unique signatures and has defined the molecular events that are involved. It is important to understand which signals from the body communicate with the brain to control our normal physiology, but also the role these signals play in disease states with the goal of targeting some of these pathways for therapeutic interventions. These signals include hormones, nutrients, and even industrial chemicals, which in turn regulate the expression of the neuropeptide genes. The Belsham laboratory delineates the molecular events that occur when neurons are activated, the cellular signaling pathways that are necessary to control gene expression, and the resulting changes in gene expression that ultimately lead to neuropeptide release in the brain and/or blood circulation, altering our physiology. For instance, the neuropeptide Y neurons, located in the region of the brain called the hypothalamus, increase feeding and if left uncontrolled can lead to obesity and its associated problems, such as diabetes and heart disease. The neuropeptide Y gene can be detrimentally activated by saturated fat and the endocrine-disrupting chemical bisphenol A. Neuropeptide Y expression is also dependent on the day-night or circadian timing system that is controlled by this same region of the brain. Normal activation of the circadian system results in whole body homeostasis or balance, but if any part of our cellular day-night control system is not working properly, desynchronization of this fine-tuned orchestra may result, leading to disease. This proposal focuses on how these neuropeptide-expressing neurons sense their environment, communicate with each other, and respond with appropriate physiological tasks and how these are altered in disease states. Dr. Belsham's innovative research program has already discovered novel control mechanisms in the brain, and these fundamental studies will provide critical knowledge about the complex nature of integrated neuroendocrine control of basic physiology.