CELL-DEATH OF SPINAL MOTONEURONS IN THE CHICK-EMBRYO FOLLOWING DEAFFERENTATION - RESCUE EFFECTS OF TISSUE-EXTRACTS, SOLUBLE-PROTEINS, AND NEUROTROPHIC AGENTS

In the absence of descending spinal and supraspinal afferent inputs, n eurons in the developing lumbar spinal cord of the chick embryo underg o regressive changes including cellular atrophy and degeneration betwe en embryonic days 10 and 16. There are significant decreases in the nu mber of motoneurons, interneurons, and sensory (dorsal root ganglion) neurons. Although there are several possible explanations for how affe rents might regulate the maintenance of neuronal viability, we have fo cused attention on the putative role of neurotrophic agents in these e vents. Previous studies have shown that specific tissue extracts (e.g. , muscle, brain), soluble proteins, growth factors, and trophic agents can promote the in vitro and in vivo survival of avian motoneurons du ring the period of natural cell death (embryonic days 6-10). Several o f these agents were also effective following deafferentation. These in cluded brain extract (BEX), muscle extract (MEX), conditioned medium f rom astrocyte cultures (ACM), as well as the following neurotrophic ag ents: nerve growth factor (NGF), brain-derived neurotrophic factor (BD NF), neurotrophin-3 (NT-3), S-100, insulin-like growth factor-I (IGF-I ), ciliary neurotrophic factor (CNTF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and leukemia inhibitory factor (CDF/LIF). Both transforming growth factor-beta (TGF-beta) and acidic fibroblast growth factor (aFGF) were ineffective. Although con siderable more work is needed to determine which (and how) specific CN S-derived trophic agents regulate motoneuron survival, the present res ults are consistent with the notion that neurotrophic agents released from or modulated by synaptic inputs to target neurons promote neurona l differentiation and survival in the CNS.