Abstract
Prostaglandin (PG) E2 acts as a pyrogenic mediator in the preoptic area (POA) probably through the EP3 subtype of PGE receptor on GABAergic neurons, and this action triggers neural pathways for sympathetic thermogenesis in peripheral organs including brown adipose tissue (BAT). To explore pyrogenic efferent pathways from the POA, we determined projection sites of EP3 receptor-expressing POA neurons with a focus on rat hypothalamic regions including the dorsomedial hypothalamic nucleus (DMH), which is a center for autonomic responses to stress. Our retrograde tracing revealed projections of EP3 receptor-immunoreactive POA neurons to the DMH, dorsal hypothalamic area (DH), and lateral hypothalamic area (LH). Bilateral microinjections of a GABAA receptor agonist into the DMH and DH, but not those into the LH, inhibited thermogenic (BAT sympathetic nerve activity, BAT and core body temperatures, and expired CO2) and cardiovascular (arterial pressure and heart rate) responses to an intra-POA PGE2 microinjection. Further immunohistochemical observations showed close association of POA-derived GABAergic axon swellings with DMH neurons projecting to the medullary raphe regions where thermoregulatory sympathetic premotor neurons are localized. These results suggest that the direct projection of EP3 receptor-expressing POA neurons to the DMH/DH region mediates febrile responses via a GABAergic mechanism. Supported by NIH and MEXT-Japan.
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