Reversible changes in the accumulation and activities of tyrosine hydroxylase and dopamine-beta-hydroxylase in neurons of nucleus locus coeruleus during the retrograde reaction.

To examine the biochemical events associated with the retrograde reaction in central noradrenergic neurons, changes in the activities of several enzymes subserving the metabolism of catecholamines, including tyrosine hydroxylase (TH),dopamine-beta-hydroxylase (DBH), DOPA decarboxylase (DDC), and monoamine oxidase (MAO), were measured in the nucleus locus coeruleus of rat brain following transection of the ascending axons from neurons in this nucleus by electrolytic lesions of the posterolateral hypothalamus. Such lesions produced a triphasic response in the activities of TH and DBH consisting of: (a) an increase to approximately 150 percent of control during the first 48 h followed by (b) a reduction reaching 60 percent of control by day 14, and (c) a full recovery of activity by day 21-28. In contrast, the activities of DDC and MAO, enzymes non-specific for catecholamine neurons, were unchanged. Immunochemical titration with specific antibodies to TH and DBH demonstrated that the fall in enzyme activity was entirely attributable to reduced accumulation of specific enzyme protein and not inhibition of pre-existing enzyme molecules. There was no reduction in the number of neurons in the nucleus locus coeruleus as a consequence of the lesion. We conclude that a reduction in the accumulation of specific enzymes subserving transmitter biosynthesis characterizes a reversible retrograde reaction of central noradrenergic neurons. The coincidence of the time course of reduced enzyme accumulation with regenerative sprouting from damaged noradrenergic axons and also the absence of classical signs of chromatolysis in locus coeruleus neurons following comparable lesions suggest that, first, during the retrograde reaction there may be a reordering of priorities governing accumulation of specific proteins favoring accumulation of those required for reconstitution of cellular processes by sprouting at the expense of proteins utilized in the synthesis of neurotransmitters, and second, some intrinsic neurons of the CNS may undergo reversible biochemical changes of a retrograde reaction in the absence of the classical morphological appearance of chromatolysis.