G.D.H. and J.L.N. contributed equally to this work.
Glutamate-mediated excitotoxicity in neonatal hippocampal neurons is mediated by mGluR-induced release of Ca++ from intracellular stores and is prevented by estradiol
Article first published online: 11 DEC 2006
European Journal of Neuroscience
Volume 24, Issue 11, pages 3008–3016, December 2006
How to Cite
Hilton, G. D., Nunez, J. L., Bambrick, L., Thompson, S. M. and McCarthy, M. M. (2006), Glutamate-mediated excitotoxicity in neonatal hippocampal neurons is mediated by mGluR-induced release of Ca++ from intracellular stores and is prevented by estradiol. European Journal of Neuroscience, 24: 3008–3016. doi: 10.1111/j.1460-9568.2006.05189.x
Present address: Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road. N.W., Room WG 03, Washington D.C., 20057, USA.
- Issue published online: 11 DEC 2006
- Article first published online: 11 DEC 2006
- Received 22 May 2006, revised 6 September 2006, accepted 21 September 2006
- excitatory amino acids;
- metabotropic receptors;
- perinatal brain injury;
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.