Inhibition of the regenerative growth of central noradrenergic neurons by intracerebrally administered anti-NGF serum

Abstract

The regenerative growth of central monoamine neurons in the adult rat brain, into an autologous iris transplant placed in the caudal diencephalon, was studied. One injection of 2 μl of anti-NGF serum, given intracerebrally close to the ascending noradrenergic axons from the locus coeruleus, caused a marked reduction in the regrowth of new axonal sprouts into the transplant, as observed 2 weeks after operation. The inhibitory effect was pronounced when the injection was given at the time of transplantation (which was also the time of axonal damage), and it was considerably less effective when given 4 days after the transplantation, i.e. at a time when the sprouting from the lesioned axons had already started. A similar inhibition of the regrowth of the lesioned noradrenergic locus coeruleus axons was also obtained after preincubation of the iris transplant in the anti-NGF serum. In contrast, the regrowth from the lesioned dopamine and indolamine fibers in the medial forebrain bundle system seemed unaffected. None of the inhibitory effects was seen in the control specimens treated with different types of control sera. This indicates that the observed impairment of the formation and regrowth of new axon sprouts from lesioned central noradrenergic neurons was the result of a specific action of the NGF-antibodies by an interference with NGF (or an NGF-like substance) in the brain tissue and/or in the transplanted iris tissue. These observations point to a possible role of endogenous NGF, or an NGF-like substance, in adult central noradrenergic neurons during regeneration.