Differential DNA damage in response to the neonatal and adult excitotoxic hippocampal lesion in rats.
We examined the developmental profile of excitotoxin-induced nuclear DNA fragmentation using the transferase dUTP nick-end labelling (TUNEL) technique, as a marker of DNA damage and cell death in rats with neonatal and adult excitotoxic lesions of the ventral hippocampus. We hypothesized that infusion of neurotoxin may result in a differential pattern of cell death in neonatally and adult lesioned rats, both in the infusion site and in remote brain regions presumably involved in mediating behavioural changes observed in these animals. Brains of rats lesioned at 7 days of age and in adulthood were collected at several survival times 1-21 days after the lesion. In the lesioned neonates 1-3 days postlesion, marked increases in TUNEL-positive cells occurred in the ventral hippocampus, the site of neurotoxin infusion, and in a wide surrounding area. Adult lesioned brains showed more positive cells than controls only at the infusion site. In the lesioned neonates, TUNEL-labelled cells were also present in the striatum and nucleus accumbens 1 day postlesion but not at later survival times. Our findings indicate that cell death in remote regions is more prominent in immature than adult brains, that it may lead to distinct alterations in development of these brain regions, and thus may be responsible for functional differences between neonatally and adult lesioned rats.
Khaing
Z Z
ZZ
National Institute of Mental Health, IRP, Clinical Brain Disorders Branch, Building 10, Room 4N306, Bethesda, MD 20892, USA.
Weickert
C S
CS
Weinberger
D R
DR
Lipska
B K
BK
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D004249:DNA Damage; D053938:DNA Fragmentation; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D007051:Ibotenic Acid / Q000633:toxicity*; D020287:In Situ Nick-End Labeling; D009714:Nucleus Accumbens / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D007051:Ibotenic Acid