Age influences the expression of GAP-43 in the rat hippocampus following seizure.
BACKGROUND
Normal aging is associated with impairments in learning and memory and motor function. One viable hypothesis is that these changes reflect an age-related decrease in brain plasticity.


OBJECTIVE
The aim of the present study was to identify age-related changes in the time course of expression of the axonal growth associated protein 43 (GAP-43) in a rat model of brain plasticity.


METHODS
We examined by Northern blotting, in situ hybridization, and immunohistochemistry the effects of age on the time course of the expression GAP-43 following pentylenetetrazole-induced seizure in the hippocampus of 3-, 18-, and 28-month-old rats.


RESULTS
In this model of brain plasticity, young rats displayed a decrease in GAP-43 mRNA levels in CA1, CA3, and polymorphic regions, lasting from 10 h to 3 days after seizure. This was followed by recovery, with peak expression between days 10 and 20. The baseline levels of GAP-43 mRNA decreased with age, especially in the CA3 region. Despite lower baseline levels, middle-aged rats showed the same pattern of upregulation of GAP-43 mRNA expression as the young animals. Old rats showed only minimal upregulation, however, and this occurred only in the polymorphic layer. The level GAP-43 protein itself was higher in old control rats than in the other two control groups, a condition that was transiently reversed by seizure activity.


CONCLUSIONS
Middle-aged rats are still capable of a sustained, though diminished, response to seizure activity, while old rats lose this ability. Disruption of the temporal and anatomical coordination of expression of GAP-43 may contribute to the general decline in brain plasticity with age.
Department of Neurology, Ernst Moritz Arndt University, Greifswald, Germany.
H
H
Schmoll
S
S
Ramboiu
D
D
Platt
J G
JG
Herndon
Ch
Ch
Kessler
A
A
Popa-Wagner
D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D003292:Convulsants; D019922:GAP-43 Protein / Q000096:biosynthesis* / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D023421:Models, Animal; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D010433:Pentylenetetrazole; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*
D003292:Convulsants; D019922:GAP-43 Protein; D012333:RNA, Messenger; D010433:Pentylenetetrazole