Influence of heat exposure on the activation of c-Fos and up-regulation of glutamate receptor subunits in rat hypothalamus

Date of Completion

January 2006

Keywords

Biology, Neuroscience|Biology, Animal Physiology

Degree

Ph.D.

Abstract

The major heat associated physiologic findings of our heat exposure model included a sustained increase in intraabdominal temperature (Tab) of 0.8°C and decrease in heart rate of 13.2% from baseline by the second day. Other major findings included continuing decrease in body weight coincidental with an increased hematocrit and plasma solute concentration indicating extracellular water loss and plasma volume reduction. These data illustrated that our rat model generated a stimulus, heat exposure, which significantly increased body temperature associated with moderate heat-induced dehydration. These major physiologic stressors were hypothesized to promote neurobiological changes in the hypothalamic nuclei, including differential activation of c-Fos and differential upregulation of ionotropic glutamate receptor subunit expression. Our quantitative data provided support for this hypothesis, suggesting that Fos and iGluRs expression are involved in the neurobiological response to moderate heat exposure. Increased Fos expression indicative of gene activation was shown in the median preoptic nucleus (MnPO) and supraoptic nucleus (SON) associated with highly significant increases in the AMPA receptor subunit GluR1. In the MnPO, these data suggested potentially enhanced signaling through the MnPO in light of the increased combined thermal and osmotic challenges, alternatively these data might indicate the potential for excessive Ca 2+ influx leading to excitotoxicity. Increased potentially glial immunostaining of GluR1 in the SON, could suggest a glial-based scavenging mechanism for excessive intraneuronal Ca2+, which might enhance homeostasis during excitotoxic conditions and indicate a neuroprotective mechanistic process facilitating osmosensitive neurotransmission and function. ^ In conditions of increased or excessive synaptic excitability, NR1-NR2B receptors primarily of extrasynaptic location would be activated, promoting excessively increased intracellular Ca2+ concentrations, and excitotoxicity, thus promoting apoptotic processes and cellular death. Taken together, these data suggest that heat exposure in our animal model is associated with differential changes in expression of glutamate receptor subunit, which may activate either intracellular survival (neuroprotective) or apoptotic cell death processes (neurotoxicity) within the hypothalamus. The balance of these processes could determine cell fate and system integrity. Potential mechanisms of cellular injury in the hypothalamus, could lead to dysfunction of the thermo- and osmoregulatory systems, which may be involved in heat illnesses, such as heat stroke. ^

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