The Effect of Heat Exposure in Rat Hypothalamus
Name: Mark Larsen
Rank: CDR, USN
Organization: University of Connecticut
Performance Site: University of Connecticut
Year Published: 2004
Abstract Status: Initial
The overall objective of this research is to generate a greater understanding of the synaptic and neuronal effects of heat acclimation. These experiments will test the central hypothesis of this proposal that: heat acclimation is associated with synaptic and/or neuronal changes in the rat hypothalamus. The specific aims of this proposal are: 1) To determine whether the expression of glutamate neurotransmitter receptors (receptor types: NMDA and AMPA) of neurons in hypothalamic nuclei are affected by heat acclimation; and 2) To determine whether intracellular signaling molecules (Fos, P-CREB) in hypothalamic neurons are affected by heat acclimation. Thus, a total of up to 70 male untrained Sprague-Dawley rats, weighing 275-300g, will be randomly assigned to one of five groups: a) control, 22▒ 1░ Celsius (C) environmental temperature and no opportunity for exercise; b) a two-day short-term heat acclimation (STHA) of up to 34░ C; c) STHA with exercise wheel applied to cage during the dark phase of the day-night cycle (STHE), d) 30-day long-term heat acclimation (LTHA) of up to 34░ C; and e) LTHA with the exercise wheel period (LTHE). Daily measures of fluid intake, animals' health and weight will be obtained. Core body temperature and relative activity will be monitored by implanted brain or intraperitoneal transmitter probes. The exercise wheel made available to some animals will allow computer monitoring of activity. Following the conclusion of their heat acclimation period, a heat response test at 40░ C, adapted from Horowitz et al, will be performed for all animals. Pre-and post-testing blood samples will be obtained for determination of hemoglobin (Hb), hematocrit, and plasma cortisol. Upon conclusion of the heat response test, the animals will be anesthetized, and undergo intracardiac perfusion with fixative and appropriate euthanasia. Brain tissue will be removed, cyroprotected, and stored at -70░ C for later analysis. Brain tissue analyses will include immunohistochemistry to determine expression of 72-kilo Dalton (kDa) heat shock protein (HSP72), a general indicator of cellular stress; and glutamate receptors (AMPA and NMDA). Immunocytochemistry will be used to determine expression of neuronal activation molecules, both Fos protein and P-CREB.