Masha Prager-Khoutorsky

Research Area: Neurophysiology / Cell & Molecular Biology Research Description: A major focus of our research is to understand integrative mechanisms by which the brain regulates basic functions of the body, such as hunger, thirst, and hormonal levels. The area of the brain involved in this control is the hypothalamus, which coordinates neuroendocrine system, cardiovascular system, energy metabolism, fluid homeostasis, and sleep. We are particularly interested in mechanisms by which specific hypothalamic areas communicate with the periphery to detect the levels of circulating molecules (metabolites, ions, and hormones) and to generate adaptive responses to adjust the physiological needs of the organism. Disruption of these mechanisms can lead to pathological conditions such as hypertension, obesity, and diabetes. The major research focus of the lab: 1. Cellular and molecular mechanisms underlying plasma sodium detection by the brain and their role in the salt-sensitive hypertension. 2. The role of non-neuronal cells (tanycytes, astrocytes, and endothelial cells) in the regulation of the blood brain barrier to mediate communication between the brain and the periphery. 3. Cellular and molecular mechanisms underlying the regulation of the blood brain barrier by the brain’s biological clock and their role in metabolic disorders. To address these questions we use a wide range of methodologies: - Patch clamp electrophysiological recordings (brain slices, dissociated cells) - Superresolution imaging - Live cell imaging (calcium, cytoskeleton, and signaling molecules) - Immunohistochemistry, histology, and neuronal-glial-vasculature morphometry - Hemodynamic measurements (blood pressure and heart rate) - Animal models of human diseases

Gu N, Makashova O, Laporte C, Chen CQ, Li B, Chevillard PM, Lean G, Yang J, Wong C, Fan J, Sharif B, Puche Saud S, Hubacek M, Choe KY, Khoutorsky A, Bourque CW, Prager-Khoutorsky M. Microglia regulate neuronal activity via structural remodeling of astrocytes. Neuron. 2025 Aug 19; doi:10.1016/j.neuron.2025.07.024. Hooshmandi M, Ho-Tieng D, Lister KC, Cai W, Wong C, Brown N, Fan J, Volodya H, Uttam S, Prager-Khoutorsky M, Sonenberg N, Gkogkas CG, Khoutorsky A. Postnatal downregulation of Fmr1 in microglia promotes microglial reactivity and causes behavioural alterations in female mice. Mol Autism. 2025 Mar 7;16(1):17. doi: 10.1186/s13229-025-00648-2. Zhou S, Makashova O, Chevillard PM, Josey V, Li B, Prager-Khoutorsky M. J Neuroendocrinol 2024 Apr;36(4):e13377. doi: 10.1111/jne.13377.