EXPRESSION OF IMMEDIATE-EARLY GENE PROTEINS FOLLOWING AXOTOMY AND INHIBITION OF AXONAL-TRANSPORT IN THE RAT CENTRAL-NERVOUS-SYSTEM

The expression of the immediate early gene-encoded proteins c-Jun, Jun B, Jun D, c-Fos, Fos B and Krox-24 in central neurons following trans ection of, or inhibition of, axonal transport in their axons was inves tigated in the rat using immunocytochemistry. Transection of the media l forebrain bundle, which produces an essentially complete axotomy of neurons in the ipsilateral mammillary nucleus, substantia nigra pars c ompacta, ventral tegmental area and parafascicularis, induced the expr ession of c-Jun, Jun D and, to a lesser extent, Krox-24, in these nucl ei. Microinjection of colchicine into the medial forebrain bundle to c hemically inhibit axonal transport similarly induced the expression of these proteins in these areas. The expression of the proteins was fir st evident 24 h after transection, reached a maximum at 48 h and was s till present after 10 days. However, after 30 days the proteins were a bsent from the substantia nigra, ventral tegmentum and parafasciculari s, and were still present only in the mammillary nuclei. The other imm ediate early genes, Jun B, c-Fos and Fos B, were never expressed above the basal levels seen in untreated rats. Transection of the corpus ca llosum and the hippocampal commissure, which produces only a partial a xotomy of neurons in the cerebral cortex and hippocampus, respectively , did not induce the expression of any of the genes in these neurons. Microinjection of colchicine or vinblastine to produce a localized inh ibition of axonal transport in the cerebral cortex, hippocampus, thala mus and cerebellum also induced the expression of c-Jun, Jun D and, ag ain to a lesser extent, Krox-24, in neurons surrounding the injection site. In contrast to this selective expression, administration of the neuronal excitant metrazole induced the expression of all six immediat e early gene proteins in central nervous system neurons.