Glutamate-mediated Excitotoxicity in Neonatal Hippocampal Neurons is Mediated by MGluR-induced Release of Ca++ from Intracellular Stores and is Prevented by Estradiol

Overview

Journal Eur J Neurosci

Specialty Neurology

Date 2006 Dec 13

PMID 17156362

Citations 45

Authors

Genell D Hilton

Joseph L Nunez

Linda Bambrick

Scott M Thompson

Margaret M McCarthy

Affiliations

Soon will be listed here.

Abstract

Hypoxic/ischemic (HI) brain injury in newborn full-term and premature infants is a common and pervasive source of life time disabilities in cognitive and locomotor function. In the adult, HI induces glutamate release and excitotoxic cell death dependent on NMDA receptor activation. In animal models of the premature human infant, glutamate is also released following HI, but neurons are largely insensitive to NMDA or AMPA/kainic acid (KA) receptor-mediated damage. Using primary cultured hippocampal neurons we have determined that glutamate increases intracellular calcium much more than kainic acid. Moreover, glutamate induces cell death by activating Type I metabotropic glutamate receptors (mGluRs). Pretreatment of neurons with the gonadal steroid estradiol reduces the level of the Type I metabotropic glutamate receptors and completely prevents cell death, suggesting a novel therapeutic approach to excitotoxic brain damage in the neonate.

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