Reactive proliferation of brain stem noradrenergic nerves following neonatal cerebellectomy in rats: role of target maturation on neuronal response to injury during development

Abstract

We sought to determine whether the reactive proliferation of noradrenergic neurons of the nucleus locus coeruleus (LC) produced in neonatal rats by systemic administration of neurotoxins is a consequence of selective damage to one or a few of the multiple projections from this nucleus. We compared the effects on some neurochemical and anatomical properties of central noradrenergic neurons of surgical interruption of projections from the LC to either cerebellum or forebrain at different times in early development of rat. Cerebellectomy performed on 3-day-old animals resulted in persistent elevations in the lower brain stem and LC, but not hippocampus in: (a) the activities of the catecholamine-synthesizing enzymes tyrosine hydroxylase (TH) and dopamine-β-hydroxylase; (b) the amounts of TH enzyme protein; (c) the V max for the high affinity uptake of [ 3H]norepinephrine in homogenates of lower brain stem; and (d) the intensity and number of catecholaminergic fluorescent terminals within the region. In contrast, hemisection of the posterior hypothalamus transecting ascending projections from the LC to forebrain failed to produce any changes in the biochemical or morphological indices of noradrenergic neuronal function in LC, lower brain stem, or cerebellum. Neither cerebellectomy nor hypothalamic lesions resulted in substantial alterations in the postnatal development of glutamic acid decarboxylase of choline acetyltransferase activity regionally in brain. The effects of cerebellectomy on TH activity in LC or brain stem were gradually lost during the first 18 days of postnatal life.