The role of Nerve Growth Factor in the Re-innervation of Denervated Skin By Sympathetic Nerves

Abstract

<p>This thesis examines the nerve growth factor (NGF) dependency of collateral sprouting (the growth of undamaged axons) and axonal regeneration (the growth of damaged axons) by sympathetic nerves in the adult rat. Sympathetic pilomotor fields were revealed by the electrical stimulation of selected dorsal cutaneous nerves. After the removal of neighbouring nerves, sympathetic fibers underwent collateral sprouting, causing the pilomotor fields to expand into the surrounding deprived territory; this sprouting was completely blocked by polyclonal anti-NGF serum. Crushing a nerve eliminated its associated pilomotor field and evoked regeneration of sympathetic fibers. Anti-NGF treatment impaired neither the subsequent restoration of the pilomotor<br />field, nor its continued expansion into surrounding skin regions. A single 6-OHDA treatment, which destroys sympathetic terminals but leaves the axons damage-free, immediately eliminated or drastically reduced the size of pilomotor fields. The pilomotor field reestablished over the following 20 days, and if the surrounding nerves had<br />been surgically eliminated, they continued to expand into the surrounding denervated territory. Anti-NGF administration did not prevent the initial phase of pilomotor field recovery, but expansion ceased when the fields were about 60% of normal size. After mUltiple 6-OHDA injections however, the expansion was almost double this value before the anti-NGF treatment was able to halt it. It is concluded that, although the cellular mechanisms underlying neurite outgrowth are probably common to collateral sprouting and axonal regeneration, only the former is regUlated by NGF; the latter is driven by a NGFindependent "regeneration response" whose size is determined by the degree of axonal damage, and probably the degree of the associated cell body reaction.</p>