C-fos expression in the rat nucleus basalis upon excitotoxic lesion with quisqualic acid: a study in adult and aged animals |
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Authors: | L Giovannelli F Casamenti G Pepeu |
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Institution: | (1) Department of Preclinical and Clinical Pharmacology, University of Florence, Italy, IT |
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Abstract: | Summary. A unilateral quisqualic acid lesion was placed in the nucleus basalis magnocellularis of 3- and 24-month-old rats, and the
animals were sacrificed at different times post-surgery. The morphology and the number of the cholinergic neurons of the nucleus
basalis were analyzed by means of immunohistochemistry for cholineacetyltransferase, in order to evaluate the size and severity
of the lesion. Immunohistochemistry for the immediate early gene c-fos was also performed in order to clarify its role in
the process of neurodegeneration following the excitotoxin injection. The DNA laddering and TUNEL techniques were used to
define the type of cell death involved. At short times (4 hr) the lesion induced alterations in the morphology of cholinergic
neurons of the nucleus basalis. Subsequently, a significant decrease in the number of neurons was found in comparison to the
contralateral unlesioned side. In the older animals the loss of cholineacetyltransferase immunoreactivity had an earlier onset
(4 hr) than in the young (24 hr). C-fos expression was induced by the lesion and not by saline injection in the nucleus basalis
and in neighbouring areas of the brain as early as 4 hr after surgery. The c-fos protein was no longer present by 24 hr. Furthermore,
the c-fos gene product was consistently absent from the nuclei of cholinergic cells. The aged animals exhibited a slower and
smaller increase in c-fos as measured by counting the labelled nuclei in the injected area. Analysis of DNA fragmentation
did not provide any evidence for apoptosis as the type of cell death involved in the cholinergic degeneration. These results
indicate that the c-fos protein might have a protective role in the response to excitotoxic lesions. Furthermore, we have
shown that the aged brain displays a reduced ability to produce a c-fos-mediated plastic response to the lesion.
Received December 17, 1997; accepted February 17, 1998 |
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Keywords: | : Apoptosis choline acetyltransferase early genes excitatory amino acids |
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