Date Thesis Awarded
Honors Thesis -- Access Restricted On-Campus Only
Bachelors of Science (BS)
John D. Griffin
Randolph A. Coleman
Lisa M. Landino
In vivo evidence demonstrates that the initial febrigenic signal from the periphery is communicated to the anterior hypothalamus (AH), the thermoregulatory center of the brain, via ascending projections of the hepatic vagus nerve. The subsequent release of Norepinephrine (NE) in the AH is a key intermediary of the febrile response, resulting in two distinct phases mediated by α1 and α2 adrenoreceptors (AR). Activation of the α1 AR produces a PGE2- independent rise in body temperature, whereas α2 activation yields a biphasic response; hypothermia followed by a PGE2-dependent temperature increase (Feleder et al., 2007). What remains unknown is how these ARs modify the firing rate of thermoregulatory neurons within the AH to drive these phases and which cyclooxygenase (COX) isozyme is responsible for PGE2 production. The action of NE in the AH was tested in the present study with the selective COX-2 inhibitor Meloxicam (0.1-10 μM) by recording single-unit activity of AH neurons in a tissue slice preparation from the adult male rat, in response to temperature and the selective α1 AR agonist Cirazoline (1 μM) or the selective α2 AR agonist Clonidine (1 μM). All neurons were classified as either warm-sensitive or temperature insensitive. Warm-sensitive neurons responded to Cirazoline with a decrease in firing rate, while temperature insensitive neurons showed a firing rate increase. These findings strengthen the role of the α1 AR in quickly driving set-point temperature into a hyperthermic range to initiate fever in a PGE2- independent fashion. In contrast, warm-sensitive neurons responded to Clonidine with an increase in firing rate, while temperature insensitive neurons showed a firing rate decrease. This indicates the α2 AR may initially be driving an opposing hypothermia, but COX-2 inhibition eliminated late phase responses after α2 AR activation, suggesting that PGE2 from this pathway is responsible for sustaining the fever initiated by α1 AR.
Imbery, Terence Edward, "An Analysis of COX-2 Derived Prostaglandin E2 (PGE2) in the Alpha-1 and Alpha-2 Adrenoreceptor-Mediated Responses of Thermally Classified Neurons in the Anterior Hypothalamus" (2008). Undergraduate Honors Theses. William & Mary. Paper 810.
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