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Developmental Changes in Central Effects of PGE¦2 and the Central Expression of PGE¦2 Receptor Subtypes in Sheep
註釋PGE2 is an arachidonic acid metabolite that has diverse centrally-mediated physiological effects that are distinctly different in the fetus (inhibits breathing activity) and adult (increases breathing, heart rate, blood pressure and body temperature). In this thesis, the centrally-mediated effects of PGE 2 were examined in newborn lambs in the first two weeks of post-natal life to determine if the early neonatal period serves as a transition period from fetal to adult responses. Results show that at 5 days after birth, PGE 2 caused hypoventilation, decreased CO2 sensitivity, and transiently increased body temperature. However, by 15 days, PGE2 had little effect on ventilation, but caused pronounced febrile response similar to those of the adult. Cardiovascular responses were not observed during the first two weeks after birth. Thus, these results show that some changes in central responses to PGE2 occurred with normal development during the neonatal period. It was further hypothesized that these changes were due to changes in the expression of PGE2 receptor subtypes during development. Transcripts for all four major subtypes of the PGE2 receptor were expressed in the same anatomical brain regions of the fetal, newborn and adult sheep brain. Within the brainstem, all four EP subtypes showed transient post-natal increases in transcript levels, albeit at different ages in the medulla (5 days) and pons (15 days). Protein levels for EP1, EP3Ã and EP4 receptors did not parallel the changes in their transcript levels. In the medulla, EP4 protein levels decreased (~25%) post-natally (p