Elsevier

Brain Research Reviews

Volume 15, Issue 1, January–April 1990, Pages 41-70
Brain Research Reviews

Physiological and pathophysiological roles of excitatory amino acids during central nervous system development

https://doi.org/10.1016/0165-0173(90)90011-CGet rights and content
Under a Creative Commons license
open archive

Abstract

Recent studies suggest that excitatory amino acids (EAAs) have a wide variety of physiological and pathophysiological roles during central nervous system (CNS) development. In addition to participating in neuronal signal transduction, EAAs also exert trophic influences affecting neuronal survival, growth and differentiation during restricted developmental periods. EAAs also participate in the development and maintenance of neuronal circuitry and regulate several forms of activity-dependent synaptic plasticity such as LTP and segregation of converging retinal inputs to tectum and visual cortex. Pre- and post-synaptic markers of EAA pathways in brain undergo marked ontogenic changes. These markers are commonly overexpressed during development; periods of overproduction often coincide with times when synaptic plasticity is great and when appropriate neuronal connections are consolidated. The electrophysiological and biochemical properties of EAA receptors also undergo marked ontogenic changes. In addition to these physiological roles of EAAs, overactivation of EAA receptors may initiate a cascade of cellular events which produce neuronal injury and death. There is a unique developmental profile of susceptibility of the brain to excitotoxic injury mediated by activation of each of the EAA receptor subtypes. Overactivation of EAA receptors is implicated in the pathophysiology of brain injury in several clinical disorders to which the developing brain is susceptible, including hypoxia-ischemia, epilepsy, physical trauma and some rare genetic abnormalities of amino acid metabolism. Potential therapeutic approaches may be rationally devised based on recent information about the developmental regulation of EAA receptors and their involvement in the pathogenesis of these disorders.

Keywords

Excitatory amino acid
Development
Glutamate
N-Methyl-daspartate
Plasticity
Central nervous system
Neurotoxicity

Abbreviations

AMPA
α-amino-3-hydroxy-5-methyl-4-isoxazole proprionate
APV
2-amino-5-phosphonovaleric acid
CNS
central nervous system
DG
diacylglycerol
DGG
γ-d-glutamylglycine
EAA
excitatory amino acid
IP3
inositol-4,5-triphosphate
LTP
long-term potentiation
MK-801
(+)-5-methyl-10,11-dihydro-5H-dibenzo [a.d] cyclohepten-5,10-imine maleate
NKH
non-ketotic hyperglycinemia
NMDA
N-methyl-d-aspartate
PCP
phencyclidine PIP2 phosphatidyl-4,5-inositolbisphosphate
PND
postnatal day
PNW
postnatal week
PNY
postnatal year
TTX
tetrodotoxin

Cited by (0)