Neurochemical Research

, Volume 20, Issue 12, pp 1477–1481 | Cite as

In utero hypoxic ischemia decreases the cholinergic agonist-stimulated poly-phosphoinositide turnover in the developing rat brain

  • K. Hersey
  • Z. Y. Hu
  • J. P. Zhang
  • P. G. Rhodes
  • G. Y. Sun
Original Articles

Abstract

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.

Key Words

Poly-PI turnover in utero hypoxic-ischemia developing brain cholinergic agonist carbachol 

Abbreviations

HI

hypoxic-ischemia

poly-PI

poly-phosphoinositides

IP

inositol monophosphate, lithium

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Copyright information

© Plenum Publishing Corporation 1995

Authors and Affiliations

  • K. Hersey
    • 1
    • 4
  • Z. Y. Hu
    • 1
    • 2
  • J. P. Zhang
    • 2
  • P. G. Rhodes
    • 3
  • G. Y. Sun
    • 2
  1. 1.Department of Child HealthUniversity of MissouriColumbia
  2. 2.Department of BiochemistryUniversity of MissouriColumbia
  3. 3.Division of Newborn Medicine, Department of PediatricsThe University of Mississippi Medical CenterJackson
  4. 4.Neonatal Intensive Care UnitPortsmouth Naval HospitalPortsmouth

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