Changes in the development of central noradrenaline neurons after neonatal axon lesions

Abstract

The effects of early surgical lesions of ascending noradrenaline (NA) axons and 6-hydroxydopamine (6-OHDA) induced NA denervation of the spinal cord on the postnatal development of central NA neurons of the rat have been studied using histo- and neurochemical techniques. The lesions were performed during the first week after birth and analyzed at the age of one or two weeks or in the adult stage. Complete unilateral hemisection at the mesencephalic level in the neonatal stage produced marked reductions of the 3H-NA uptake in vitro in the cerebral cortex with concomitant significant increases (+30–50%) of the uptake on the ipsilateral side of the ponsmedulla when determined in adulthood. Partial unilateral hemisection, restricted to produce an axotomy of the dorsal NA bundle, led to almost complete NA depletions in the cerebral cortex, while significant NA elevations were found in the mesencephalon (+25–40%), pons-medulla (+15%) and cerebellum (+90%) on the ipsilateral side. In the latter region a significant NA increase (+50%) was also observed in the controlateral side. Regional analysis of the 3H-NA uptake after partial hemisection gave similar results. Intraspinal injection of 6-OHDA on the day of birth resulted consistently in marked NA depletions (−90% or more) in the spinal cord, while the effects on NA in the cerebral cortex varied, being either unaffected or markedly reduced. Animals with unaffected cerebral cortex disclosed a significant NA increase in the pons-medulla only, whereas animals with cortical NA denervation displayed significant increases in endogenous NA levels both in the pons-medulla and the cerebellum. The present results give further support for the “pruning effect” concept explaining the growth response that central NA neurons exhibit after neonatal 6-OHDA treatment systemically or when one axonal branch is damaged neonatally.