1. Cellular and molecular mechanisms underlying plasma sodium detection by the brain and their role in the salt-sensitive hypertension. Specifically, we study a function of specialized osmosensory neurons that are activated by increased levels of sodium in the blood. These neurons release antidiuretic hormone vasopressin to stabilize the levels of sodium and water in the circulation. We investigate the role of unique cytoskeletal structures and signalling molecules featured by these neurons, and study how these elements are affected by high dietary salt, mediating hyperactivation of osmosensory neurons, and thereby contributing to hypertension.
2. Cellular and molecular mechanisms underlying the communication between the brain and the peripheral circulation: the role of non-neuronal cells (tanycytes, astrocytes, and endothelial cells) in the regulation of the blood brain barrier. Metabolites, hormones and other circulating molecules cannot freely penetrate into the brain due to the existence of the blood brain barrier, which isolates the brain from molecules found in the peripheral circulation. Specialized small brain regions in the hypothalamus (called circumventricular organs) are lacking the complete blood brain barrier. Therefore, blood-borne circulating molecules can partially access these areas to influence the activity of local neurons, which in turn generate neuronal responses by mediating hormonal release, promoting behaviors (e.g. by triggering thirst or hunger), or activating autonomic nerve system to modulate cardiovascular system and renal function. Our goal is to understand the cellular and molecular mechanisms that regulate the access of peripheral signals to neurons in the circumventricular organs and to study functions of non-neuronal cells (tanycytes, astrocytes, and endothelial cells) in this dialogue between the periphery and the central nervous system.
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. Brain’s biological clock generates circadian rhythms and influences a variety of processes in the brain and the body. Our goal is to understand how the biological clock regulates the access of nutrients from the peripheral circulation (e.g. metabolites, ions, hormones, and peptides) into the brain. We investigate the role of circadian modulation of the blood brain barrier permeability on central control of energy metabolism and cardiovascular function. We study how this mechanism affects metabolic/nutrient signals in the brain and periphery, and how a perturbation in nutrient access timing (shifting food intake from the active hours to the sleep period) can promote obesity, metabolic syndrome, and diabetes.
To address these questions, we use a variety of techniques:
- 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