J Korean Pediatr Soc.  2000 Jan;43(1):85-96.

Apoptosis, P53, bax and Bcl-2 Protein Expressions in Neonatal rat Hippocampus by Kainic Acid-induced Seizure

Affiliations
  • 1Department of Pediatrics, College of Medicine, Chung-Ang University, Seoul, Korea.

Abstract

PURPOSE: Apoptosis is a process of active cell death which has been suggested to be part of hippocampal cell loss caused by kainic acid (KA). Immature rats showed higher susceptibility and mortality to KA but did not develop recurrent seizure, long term behavioral or neuropathologic changes. We investigated whether this was due to age-dependent resistance, and elucidated the molecular mechanics which mediate P53-induced apoptosis, identifying bax and bcl-2 as P53 protein expressions that serve as a paradigm on how the balance of bcl-2 to bax is differentially altered by apoptotic stimuli.
METHODS
Sprague-Dawley rats were classified into postnatal age (P) 10, 15, 20 and 30 days and given specific doses of i.p. KA (P10; 3mg/kg, P15; 4mg/kg, P20; 8mg/kg, P30; 10mg/kg). Only rats that achieved continuous clonic seizure were selected and decapitated at 24, 48, and 72h (n=15 each age). We analysed P53, bax and bcl-2 protein expressions by immunohistochemistry as well as apoptosis by TUNEL in each group.
RESULTS
KA-induced hippocampal cell death first appeared in P20. Remarkable expressions of apoptosis, P53 and bax, while bcl-2 proteins were suppressed were observed at 48 hours following KA in P20 and the most prominently affected areas were hippocampal CA1 and CA3 neurons. Similar results were obtained in P30. CONCLUSOIN: A Induction of P53, a growth regulatory gene which has been implicated in apoptosis and the changes in bcl-2 to bax ratio may be important to KA mediated excitotoxicity of specific regions during the critical period of developing rat brain.

Keyword

Kainic acid (KA); Hippocampus; Immature rat; Apoptosis; P53; Bax; Bcl-2 protein expression

MeSH Terms

Animals
Apoptosis*
Brain
Cell Death
Critical Period (Psychology)
Genes, Regulator
Hippocampus*
Immunohistochemistry
In Situ Nick-End Labeling
Kainic Acid
Mechanics
Mortality
Neurons
Rats*
Rats, Sprague-Dawley
Seizures*
Kainic Acid
Full Text Links
  • KJP
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
    DB Error: unknown error