Interaction between serotonergic and noradrenergic axons during axonal regeneration

The present experiments focused on the morphological interaction between serotonergic (5-HT) and noradrenergic (NA) axons during regeneration following partial axonal denervation in the cerebral cortex in adult rats. The denervation paradigm used employed two neurotoxins, one for 5-HT and one for NA axons, infused together at one cortical site while a single neurotoxin to either 5-HT or NA was infused at the symmetrical cortical site in the other hemisphere. This treatment enabled us to assess the role of 5-HT or NA axons in the regeneration of the other monoaminergic axon. 5-HT axon regeneration became apparent as early as 28 days after the toxin injection, whereas the regeneration of NA axons was not evident even at 60 days after the toxin injection. Since NA axons revealed marked regeneration in the cortical site with denervation of 5-HT axons, intact 5-HT axons may be inhibitory on the regeneration of NA axons. In contrast, since the regeneration of 5-HT axons was suppressed in the absence of NA axons, NA axons appear to exert a facilitatory effect on 5-HT axon regeneration. These results suggest that the role of 5-HT axons in the regeneration of NA axons is opposite to that of NA axons in the regeneration of 5-HT axons. In addition, the regeneration of 5-HT axons occurred much faster than that of NA axons in response to axonal damage. The differential roles of 5-HT and NA axons in axonal regeneration may play a role in a variety of physiological functions related to these monoamines and possibly in the pathophysiology of clinical depression.