CAREER: Hypothalamic Tanycytes and Neuronal Plasticity in the Regulation of Energy Balance

Ohio State University, The, Columbus OH

Investigators

Abstract

The regulation of energy balance requires communication and coordination with the hypothalamus, arguably the most important brain region for maintaining energy balance and where nutritional signals and appetite pathways converge on energy expenditure circuitry. One specialized cell type in the hypothalamus that is not well understood at the mechanistic level is the tanycytes, a putative stem cell population that lines the interface between the hypothalamus and one of the brain's internal ventricles. Tantycytes are able to sense factors circulating in the cerebrospinal fluid (CSF) and are important for glucose sensing and exhibit the ability to change and regenerate, but the signaling pathways that regulate these characteristics are not well understood. Using approaches to mark and lineage-trace developing cells in the adult brain, this project aims to understand tanycytes and their ability to renew adult hypothalamic neurons in response to varying conditions of energy balance. The project includes studies to elucidate the role of particular growth factor signaling pathways in tanycytes in enabling this regenerative ability of hypothalamic neurons in the adult brain. The broader impacts of this project include a formal senior Capstone course for students working conducting their senior thesis research under this project, and, to increase access to scientific careers in general, a week-long course on in the local community college system that covers and that can bridge to a summer fellowship in the laboratory of the principal investigator of this project. Numerous metabolic interventions, such as exercise or caloric restriction, are thought to impact neural plasticity in the hypothalamus, or the brain's command center for regulating energy balance. In particular, the tanycytes that line the hypothalamic third ventricle are thought not only to mediate communication between hypothalamic nuclei and circulating factors in the cerebrospinal fluid, but also to act as adult neural stem cells, replacing hypothalamic nuclei in response to various energetic cues. Using adult neural stem cell reporter mice developed by the principal investigator, this project examines how tanycytes impact neural plasticity and energy balance regulation in the adult brain. To determine whether or not bone morphogenetic protein signaling through the type 1 receptor (BMPR1A) impacts neurogenesis in alpha or beta tanycytes, the investigators use Rax-Cre or Glast-Cre mice to ablate BMPR1A, followed by assessment of energy status and tanycyte differentiation into hypothalamic neurons. Collectively, the studies will advance understanding of key mechanisms involved in hypothalamic plasticity in response to changing energy status. This project is co-funded by the Established Program to Stimulate Competitive Research (EPSCoR) of the Office of Integrative Activities. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.