BETA-APP GENE-EXPRESSION IS INCREASED IN THE RAT-BRAIN AFTER MOTOR-NEURON AXOTOMY

The response of the betaAPP gene to neuronal injury was studied in the facial and hypoglossal nerve nuclei of the rat after corresponding nerve axotomy. Increased levels of betaAPP 695, 714, 751 and 770 mRNAs were observed after either facial or hypoglossal nerve axotomy in the parent ipsilateral motor neurons. The increase was gradual, with maximal values 7 days after axotomy. BetaAPP mRNA expression returned to normal values 60 days after the lesion. Increased betaAPP immunostaining was also detected in ipsilateral chromatolytic motor neurons. No change in betaAPP immunoreactivity was observed in oligodendrocytes, another cell type expressing betaAPP under normal conditions. A rapid increase in the expression of the GFAP gene was observed in reactive astrocytes surrounding chromatolytic neurons in the ipsilateral facial or hypoglossal nuclei. Thus, in contrast with other models of neuronal injury, where only the Kunitz protease inhibitor-containing betaAPP mRNA isoforms are increased, all betaAPP mRNAs are increased in the axotomy model. Furthermore, although betaAPP expression has been shown to be increased in reactive astrocytes following neuronal injury, in the present study the increase was essentially found in the motor neurons reacting to axotomy.