NMDA POTENTIATES NGF-INDUCED SPROUTING OF SEPTAL CHOLINERGIC FIBERS

NERVE growth factor (NGF) injected into the otherwise unlesioned adult rat septum induced sprouting of presumptive cholinergic fibres positi ve for p75(NGFR) and acetylcholinesterase (AChE). These fibres did not stain for tyrosine hydroxylase and therefore did not represent sympat hetic ingrowth. Neurofilament staining on adjacent sections revealed f ibres with similar morphology, suggesting new outgrowth in the form of sprouting rather than the upregulation of p75(NGFR) and AChE in pre-e xisting fibres. Simultaneous injections of subneurotoxic doses of N-me thyl-D-aspartate (NMDA) significantly potentiated the effect of NGF on cholinergic fibre sprouting and caused pronounced glial fibrillary ac idic protein (GFAP)positive astrocytosis. Application of NMDA alone di d not elicit sprouting of this type. These findings indicate that NGF can induce the sprouting of uninjured adult rat septal cholinergic fib res in vivo and suggest that reactive astrocytes are not inhibitory to cholinergic axonal outgrowth, and might serve as a substrate for grow ing axons in the presence of NGF.