SPROUTING ADULT CNS CHOLINERGIC AXONS EXPRESS NILE AND ASSOCIATE WITHASTROCYTIC SURFACES EXPRESSING NEURAL CELL-ADHESION MOLECULE

To assess the cellular and molecular substrates for cholinergic axon g rowth in the adult central nervous system (CNS), we implanted grafts o f control and nerve growth factor (NGF)-producing genetically modified fibroblasts within the striatum of rats. Sprouting cholinergic axonal processes that grew into grafts of NGF-producing fibroblasts were fas ciculated and followed the surface of astrocytic processes for long di stances within the grafts. The close and long distance anatomical rela tionship between the sprouted axons and the astrocytes supported previ ous ultrastructural evidence that astrocytes may serve as a cellular s ubstrate for sprouting cholinergic axons in vivo. The sprouted axon pr ocesses were associated with the expression of nerve growth factor-ind ucible large external (NILE) glycoprotein on their surfaces. NILE expr ession was not seen in control grafts where there was an absence of ch olinergic ingrowth. NILE has been demonstrated to play a role in axon fasciculation in a number of other neural systems. The astrocytic proc esses in both control and NGF-producing fibroblast grafts expressed ne ural cell adhesion molecule (NCAM), suggesting that NCAM-mediated adhe sion may be responsible for the close relationship between the axons a nd astrocytes within the grafts. NGF-induced heterotypic interactions between neuronal NILE and astroglial NCAM may also be required for adu lt cholinergic axonal sprouting. (C) 1996 Wiley-Liss, Inc.