2008 Brain Star Award Recipient - Reza Sharif-Naeni
Recipient
Reza Sharif-Naeni - Biosketch
PhD
McGill University
Article
TRPV1 Gene Required for Thermosensory Transduction and Anticipatory Secretion from Vasopressin Neurons during Hyperthermia. Sharif-Naeini R, Ciura S, Charles W. Bourque CW. Neuron 2008; 58: 179–185.
Significance of the paper
Acute and large deviations in the osmolality of extracellular fluids can have disastrous consequences for the organisms, with symptoms ranging from confusion, convulsions, coma and death. To avoid such deviations, central mechanisms that stabilize fluid osmolality have evolved to prevent water shifts that could perturb tissue function. For instance, mammals respond to a rise in core body temperature (hyperthermia) by promoting evaporative heat loss through panting and the production of sweat. Remarkably, the potential impact of this response on body fluid balance is blunted due to a simultaneous increase in the release of vasopressin (VP, the antidiuretic hormone) from the neurohypophysis. How this important anticipatory homeostatic response is achieved is not known, but previous work has indicated that a central thermosensory mechanism may be required for this effect to occur.
Our results demonstrate that hypothalamic VP neurons are intrinsically thermosensitive, and that this thermosensitivity is due to the expression of a heat-activated calcium permeable cation channel that is blocked by a selective TRPV1 channel antagonist, and is absent in VP neurons isolated from Trpv1 knockout (Trpv1-/-) mice. Unlike their wild-type (WT) counterparts, acutely dissociated VP neurons from Trpv1-/- mice could not generate increases in membrane conductance and depolarizing potentials in response to a heat stimulus (35-39 °C). These results suggest that expression of a trpv1 gene product is required for the intrinsic thermosensitivity of VP neurons.
Because the electrical activity of these cells is essential to the release of vasopressin, we speculated that the failure of VP neurons of Trpv1-/- mice to detect a hyperthermic stimulus would result in an attenuated VP release during hyperthermia in vivo. We measured the relationship between serum VP concentration ([VP]) and core body temperature in groups of control and thermally challenged WT and Trpv1-/- mice. In the WT animals, hyperthermia caused a significant increase in average serum [VP] whereas no significant change could be detected in Trpv1-/- mice. Thus, Trpv1-/- mice display a significant deficit in anticipatory VP secretion during hyperthermia.
These results are the first to suggest that expression of the trpv1 gene is essential both for thermosensory transduction in these cells and for heat-induced VP secretion in vivo.