Delayed neuronal loss after administration of intracerebroventricular kainic acid to preweanling rats

Excitotoxins, such as kainic acid (KA), have been shown to produce both imm ediate and delayed neuronal degeneration in adult rat brain. while preweanl ing 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.) administrat ion of RA would produce delayed neuronal loss, preweanling rats were admini stered 5 nmol or 10 nmol KA i.c.v. on postnatal day 7 (P7) and then examine d 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 amou nt of immunoreactivity to jun, the protein product of the immediate early g ene, c-jun, adjusted for the number of remaining neurons was increased in t he same brain areas. Antibody labeling of inducible heat shock protein and glial fibrillary acidic protein was not similarly increased in animals admi nistered 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 chat neuronal loss occurs after a delay, perhaps through apoptosis. These f indings may be relevant to the pathogenesis of neuropsychiatric disorders, such as schizophrenia, that are characterized by early limbic-cortical defi cits but onset of illness in young adulthood. (C) 1999 Elsevier Science B.V . All rights reserved.