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Glutamate‐mediated excitotoxicity in neonatal hippocampal neurons is mediated by mGluR‐induced release of Ca ++ from intracellular stores and is prevented by estradiol
Author(s) -
Hilton Genell D.,
Nunez Joseph L.,
Bambrick Linda,
Thompson Scott M.,
McCarthy Margaret M.
Publication year - 2006
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2006.05189.x
Subject(s) - kainic acid , metabotropic glutamate receptor , glutamate receptor , excitotoxicity , nmda receptor , kainate receptor , metabotropic glutamate receptor 1 , neuroscience , long term depression , ampa receptor , metabotropic receptor , metabotropic glutamate receptor 5 , hippocampal formation , chemistry , biology , receptor , biochemistry
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.