Axonal regeneration of peripheral adrenergic neurons: effects of antiserum to nerve growth factor in mouse.

Abstract

The effect of the antiserum to Nerve Growth Factor (NGF) on the regrowth of adrenergic axons following 6-hydroxydopamine-(6-OH-DA)induced axotomy was investigated in the mouse using fluorescence histochemistry and determinations of endogenous NA. A single subcutaneous injection of 0.1 ml/g of anti-NGF serum, given one day after the 6-OH-DA-injection (60 mg/kg), caused a pronounced inhibition of the regeneration of the adrenergic axons in all peripheral tissues investigated (iris, salivary glands, heart, intestine, spleen and pancreas). The ganglionic cell bodies in the superior cervical ganglion underwent a marked atrophy, as observed 5 days and 3 weeks after the 6-OH-DA treatment, but they had regained normal appearance after 2 months. Furthermore, the fluorescence histochemistry revealed an antiserum-induced reduction of the NA content in all parts of the regenerating neurons, except for the most distal portions of the surviving axon stumps. At 5 days and 3 weeks after the 6-OH-DA-treatment the sprouting and regrowth of the adrenergic axons were much reduced in the anti-NGF serum-treated animals. When compared with those of the corresponding controls, the NA levels in the anti-NGF serum-treated specimens were only 20–40% at 3 weeks. The anti-NGF serum-induced inhibition was temporary, and between 3 weeks and 2 months after treatment the regeneration in the antiserum-treated animals started to catch up with the controls. The results indicate that endogenous NGF or NGF-like substances may play a role in the process of regeneration of lesioned sympathetic neurons in the adult animal. They also suggest that mature sympathetic neurons during regeneration resume the high sensitivity to, and dependence on, NGF, which otherwise are characteristic of sympathetic neurons during their ontogenetic growth and development.