Delayed neuronal loss after administration of intracerebroventricular kainic acid to preweanling rats.
Excitotoxins, such as kainic acid (KA), have been shown to produce both immediate and delayed neuronal degeneration in adult rat brain. While preweanling rats have been shown to be resistant to the immediate neurotoxicity of KA, the presence of delayed neuronal loss has not been investigated in such animals. To determine whether intracerebroventricular (i.c.v.) administration of KA would produce delayed neuronal loss, preweanling rats were administered 5 nmol or 10 nmol KA i.c.v. on postnatal day 7 (P7) and then examined at P14, P45, and P75. Using three-dimensional, non-biased cell counting, neuronal loss was observed in the CA3 subfield of the hippocampal formation at P45 and P75 in animals administered 10 nmol KA, as compared to animals administered 5 nmol KA or artificial cerebrospinal fluid. Further, the amount of immunoreactivity to jun, the protein product of the immediate early gene, c-jun, adjusted for the number of remaining neurons was increased in the same brain areas. Antibody labeling of inducible heat shock protein and glial fibrillary acidic protein was not similarly increased in animals administered i.c.v. KA. The data suggest that while i.c.v. KA does not produce immediate neuronal loss in preweanling rats, the hippocampus is altered so that neuronal loss occurs after a delay, perhaps through apoptosis. These findings may be relevant to the pathogenesis of neuropsychiatric disorders, such as schizophrenia, that are characterized by early limbic-cortical deficits but onset of illness in young adulthood.
Montgomery
E M
EM
Department of Psychology, College of Arts and Sciences, Washington University, St. Louis, MO 63110, USA.
Bardgett
M E
ME
Lall
B
B
Csernansky
C A
CA
Csernansky
J G
JG
D000375:Aging / Q000502:physiology; D000818:Animals; D000833:Animals, Suckling / Q000254:growth & development / Q000502:physiology*; D002452:Cell Count / Q000187:drug effects; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors