DIFFERENTIAL EXPRESSION OF ALPHA-CGRP AND BETA-CGRP GENES WITHIN HYPOGLOSSAL MOTONEURONS IN RESPONSE TO AXOTOMY

In this study we have analysed, by in situ hybridization, the expressi on of the genes for both alpha-CGRP and beta-CGRP in hypoglossal motor nuclei following transection of the left hypoglossal nerve. Our resul ts show that the gene for alpha-CGRP displays a peculiar sequence of r egulation (a successive up-down-up-recovery sequence) within ipsilater al hypoglossal motoneurons in response to axotomy. It is initially up- regulated, then down-regulated (displaying mRNA levels below basal), a nd later again up-regulated before recovery. By contrast, the gene for beta-CGRP displays a successive and distinct up-down-recovery sequenc e of regulation (it does not display a second increase in mRNA product ion). The first up-regulation of the alpha-CGRP gene occurs just durin g the early period of perineuronal glial reaction and the second up-re gulation just during the period of delayed astrocyte reaction and musc le reinnervation. Because alpha-CGRP is a neuron-derived factor for ma ny types of cells, including astrocytes and skeletal myocytes, our res ults suggest that the pleiotropic alpha-CGRP may be a motoneuron-deriv ed trophic signal for both glial and skeletal muscle cells in order to maintain the motoneuron itself and, in consequence, might be of thera peutic interest in treating degenerative diseases of motoneurons. beta -CGRP might be redundant within the hypoglossal motoneurons.