DEGENERATIVE PHENOMENA AND REACTIVE MODIFICATIONS OF THE ADULT-RAT INFERIOR OLIVARY NEURONS FOLLOWING AXOTOMY AND DISCONNECTION FROM THEIR TARGETS

Adult olivocerebellar axons are capable of vigorous regeneration when provided with growth-permissive environmental conditions. To elucidate the contribution of intrinsic properties to the regenerative capabili ties of inferior olivary neurons, we have examined the cellular modifi cations occurring in these neurons following axotomy and target depriv ation in the absence of exogenous growth-promoting influences. Axotomi zed inferior olivary neurons undergo perikaryal shrinkage, dendritic a trophy and a loss of anti-calbindin immunoreactivity. A conspicuous ce ll death occurs during the first few weeks after lesion, but about 35% of the affected neurons survive up to 60 days. Coincidentally, a subs et of the injured nerve cells become strongly reactive for NADPH diaph orase histochemistry, and this expression is correlated with survival in the medial accessory olive and in the principal olive. In addition, the affected neurons express or maintain the expression of several ma rkers related to regenerative processes, including transcription facto rs c-Jun, JunD and Krox-24, the growth-associated protein GAP-43 and t he developmentally regulated calcitonin gene-related peptide (CGRP). T he expression of all these markers is sustained up to two months after lesion, the longest survival time examined. These results show that a lthough adult axotomized inferior olivary neurons undergo severe regre ssive modifications leading to a conspicuous cell loss, at least a sub set of them is resistant to the lesion. In addition, the long-lasting expression of several axon-growth associated markers expressed in thes e neurons in response to injury reveals that they are endowed with a s trong intrinsic regenerative potential. (C) 1998 IBRO. Published by El sevier Science Ltd.