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Journal of Neuroscience, Vol 13, 4470-4485, Copyright © 1993 by Society for Neuroscience
Loss of glutamate decarboxylase mRNA-containing neurons in the rat dentate gyrus following pilocarpine-induced seizures
A Obenaus, M Esclapez and CR Houser
Brain Research Institute, University of California at Los Angeles 90024- 1761.
In situ hybridization methods were used to determine if glutamic acid
decarboxylase (GAD) mRNA-containing neurons within the hilus of the dentate
gyrus are vulnerable to seizure-induced damage in a model of chronic
seizures. Sprague-Dawley rats were injected intraperitoneally with
pilocarpine, and the hippocampal formation was studied histologically at 1,
2, 4, and 8 week intervals after pilocarpine- induced seizures. In situ
hybridization histochemistry, using a digoxigenin-labeled GAD cRNA probe,
demonstrated a substantial decrease in the number of GAD mRNA-containing
neurons in the hilus of the dentate gyrus in the pilocarpine-treated rats
as compared to controls at all time intervals. Additional neuronanatomical
studies, including cresyl violet staining, neuronal degeneration methods,
and histochemical localization of glial fibrillary acidic protein,
suggested that the decrease in the number of GAD mRNA-containing neurons
was related to neuronal loss rather than to a decrease in GAD mRNA levels.
The loss of GAD mRNA-containing neurons in the hilus contrasted with the
relative preservation of labeled putative basket cells along the inner
margin of the granule cell layer. Quantitative analyses of labeled neurons
in three regions of the dentate gyrus in the 1 and 2 week groups showed
statistically significant decreases in the mean number of GAD
mRNA-containing neurons in the hilus of both groups of experimental
animals. No significant differences were found in the molecular layer or
the granule cell layer, which included labeled neurons along the lower
margin of the granule cell layer. The results indicate that, in this model,
a subpopulation of GAD mRNA- containing neurons within the dentate gyrus is
selectively vulnerable to seizure-induced damage. Such differential
vulnerability appears to be another indication of the heterogeneity of GABA
neurons.
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