Results show an important relationship between ischemia-induced depletion of high-energy metabolites and poly-PI signaling activity. However, the uncoupling between Ins(1,4,5)P3 and ATP during reperfusion after severe ischemia suggests that metabolism of Ins(1,4,5)P3 is more stringently regulated than ATP.
Perinatal hypoxic-ischemic (HI) insult is known to cause cellular and molecular disturbances leading to functional and behavioral abnormalities during brain development. In this study, we examined the effects of an in utero HI insult on poly-phosphoinositide turnover in vivo in the cerebrum and cerebellum as well as cholinergic-stimulated turnover in cortical slices from developing rat brain. In utero HI treatment was carried out by clamping the uterine blood vessels of near-term fetuses for 5, 10 and 15 min followed by resuscitation of the newborn pups. The in vivo protocol for examining poly-PI signaling activity in 2 week-old pup brain involved intracerebral injection of [3H]inositol for 16 hr and subsequent intraperitoneal injection with lithium (8 meq/kg) for 4 hr prior to decapitation. In the control pups, lithium elicited a 2.6 fold increase in labeled inositol phosphate (IP) in the cerebrum as compared to a 1.3 fold increase in the cerebellum. In utero HI insult (5 to 15 min) resulted in a small increase in labeled IP in the cerebrum but not in the cerebellum. Carbachol stimulation of poly-PI turnover was examined in brain slices prelabeled with [3H]inositol in vivo. Incubation of the prelabeled slices with carbachol in the presence of LiCl (10 mM) resulted in a time-, dose- and age-dependent increase in labeled IP. Brain slices from 2 week-old pups that experienced in utero HI-treatment for 10 and 15 min (but not 5 min) showed a significant decrease in carbachol-stimulation of labeled IP as compared with control pups. These results indicate the effects of in utero HI on the choninergic-stimulated poly-PI signaling pathway and its implication on related functional deficits in the developing brain.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.