KAUST Research Workshop on Innovative Technologies to Study Brain Energy Metabolism
Jean-Pierre Aubert Research Center, Lille, France
Dr. Jerome Clasadonte is currently building an independent research career at Inserm. His research aims to decipher the role of the hypothalamic glial cells, tanycytes, in the control of feeding behavior, and their contribution to metabolic disorders.
It is now believed that lactate coming from glial cells is a very efficient energy fuel for neurons. Here, we propose that the activity of two distinct populations of neurons in the hypothalamus might rely on lactate trafficking through glial gap junction intercellular communications mediated by connexin (Cx) 43. We suggest that these neuroglial metabolic interactions in the hypothalamus might contribute to the regulation of sleep-wake cycle and energy homeostasis. In the first part, we focus on astrocytes from the lateral hypothalamic area (LHA), the wakefulness center of the brain. We show that knockout of astroglial Cx43 in the LHA perturbs glucose and lactate trafficking through the astroglial networks, which silences wake-promoting orexin neurons in this area and consequently causes a narcoleptic-like phenotype, characterized by excessive sleepiness and fragmented wakefulness during the nocturnal active phase. In the second part, we focus on tanycytes from the arcuate nucleus of the hypothalamus (ARH), the feeding center of the brain. Tanycytes are specialized hypothalamic glial cells found in the lateral walls of the third ventricle, with one side contacting the cerebrospinal fluid (CSF), which contains glucose, and the other sending a single process towards the ARH. We show that, like astrocytes, tanycytes are connected to each other by Cx43-mediated gap junctions. Blocking Cx43-mediated gap junctions in tanycytes perturbs trafficking of glucose between tanycytes and alters energy balance towards increased food intake and decreased energy expenditure, suggesting a role for tanycyte networks in the regulation of energy homeostasis. Current experiments are designed to determine whether this phenotype is caused by the inability of tanycyte networks to shuttle glucose-derived lactate to the satiety-promoting proopiomelanocortin (POMC) neurons from the ARH. Altogether, these results suggest that different populations of glial cells in the hypothalamus, astrocytes and tanycytes, might be metabolically coupled with specific populations of hypothalamic neurons to drive normal daily cycle of wakefulness and satiety.