Deafferentation-Induced Expression of GAP-43, NCAM, and NILE in the Adult Rat Dorsal Horn Following Pronase Injection of the Sciatic Nerve

Abstract

The expression of growth-associated protein 43 (GAP-43), neural cell adhesion molecule (NCAM), and nerve-growth-factor-inducible large external glycoprotein (NILE) in the adult rat dorsal horn was examined at several survival times after unilateral pronase injection of the sciatic nerve. Pronase injection produces a permanent major loss of sciatic primary afferents in the dorsal horn, and there is a later sprouting of saphenous afferents into the sciatic territory. Small-diameter myelinated and nonmyelinated saphenous afferents sprout within the superficial dorsal horn, and larger, myelinated afferents sprout within the deep dorsal horn. In the present study, GAP-43 and NCAM immunoreactivity increased in the superficial dorsal horn by 10 days after injection. By 20 days, the increase spread into the deep dorsal horn; NCAM returned to normal after 1-2 months, but GAP-43 persisted up to 4 months. NILE immunoreactivity appeared in laminae I and II by 10 days and increased up to 30 days; by 2 months no NILE remained. NILE never spread into the deeper dorsal horn, regardless of survival time.

These data suggest a correlation in the expression of both NCAM and NILE with the sprouting of fine-diameter sprouting afferents in laminae I and II, and of NCAM expression with the sprouting of larger-diameter afferents in the deep dorsal horn. The early appearance of GAP-43, NCAM, and NILE in laminae I and II, and delayed onset of NCAM and GAP-43 in the deeper dorsal horn, may be correlated with the early clearing of degenerated afferent terminals in laminae I and II and persistence of degenerated terminals in the deep dorsal horn that occur after primary afferent injury. The expression of GAP-43 beyond that of NCAM and NILE may indicate that once sprouted terminals are guided to their targets, further growth and maturation of the terminals take place, reaching completion by 4 months.

Key Words:

• primary afferents
• cell adhesion molecules
• axonal guidance
• plasticity
• guidance factors