Arrest of neuronal migration by excitatory amino acids in hamster developing brain.
The influence of the excitotoxic cascade on the developing brain was investigated using ibotenate, a glutamatergic agonist of both N-methyl-D-aspartate (NMDA) ionotropic receptors and metabotropic receptors. Injected in the neopallium of the golden hamster at the time of production of neurons normally destined for layers IV, III, and II, ibotenate induces arrests of migrating neurons at different distances from the germinative zone within the radial migratory corridors. The resulting cytoarchitectonic patterns include periventricular nodular heterotopias, subcortical band heterotopias, and intracortical arrests of migrating neurons. The radial glial cells and the extracellular matrix are free of detectable damage that could suggest a defect in their guiding role. The migration disorders are prevented by coinjection of DL-2-amino-7-phosphoheptanoic acid, an NMDA ionotropic antagonist, but are not prevented by coinjection of L(+)-2-amino-3-phosphonopropionic acid, a metabotropic antagonist. This implies that an excess of ionic influx through the NMDA channels of neurons alters the metabolic pathways supporting neuronal migration. Ibotenate, a unique molecular trigger of the excitotoxic cascade, produces a wide spectrum of abnormal neuronal migration patterns recognized in mammals, including the neocortical deviations encountered in the human brain.
Marret
S
S
Laboratoire de Neurologie du Développement, Hôpital Robert-Debré, Paris, France.
Gressens
P
P
Evrard
P
P
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000502:physiology*; D002454:Cell Differentiation; D002455:Cell Division; D002465:Cell Movement / Q000187:drug effects; D006224:Cricetinae; D004247:DNA / Q000032:analysis; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007051:Ibotenic Acid / Q000633:toxicity*; D008297:Male; D008647:Mesocricetus; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; C000211:2-amino-3-phosphonopropionic acid; D007051:Ibotenic Acid; D015763:2-Amino-5-phosphonovalerate; D004247:DNA; D000409:Alanine; C031231:2-amino-7-phosphonoheptanoic acid