Differential regulation of survival and growth in adult sympathetic neurons: An in vitro study of neurotrophin responsiveness

The survival and growth of embryonic and postnatal sympathetic neurons is d ependent on both NGF and NT3, While it has been established that adult sens ory neurons survive independently of neurotrophins, the case is less clear for adult sympathetic neurons, where the studies of survival responses to n eurotrophins have relied upon using long-term cultures of embryonic neurons , We have previously established a method to culture purified young (7 day) and adult (12 week) sympathetic neurons isolated from adult rat superior c ervical ganglia (SCG) in order to examine their survival and growth respons es to neurotrophins, We now show that by 12 weeks after birth virtually all neurons (90%) survive for 24 h in the absence of neurotrophins. Neuron sur vival is unaffected by treatment with anti-NGF antibodies (anti-NGF) or wit h the tyrosine kinase inhibitor, K252a, confirming the lack of dependence o n extrinsic neurotrophins. Duration of neuron survival in culture increases significantly between E19 and day 7 and week 12 posnatally, and is similar ly unaffected by the presence of anti-NGF or K252a, Saturating concentratio ns of NGF and NT3 are equipotent in promoting neurite extension and branchi ng. However, we find that NGF is more potent than NT3 in promoting neurite growth, irrespective of postnatal age, The growth-promoting effects of NGF and NT3 are almost entirely blocked by K252a, demonstrating that these effe cts are mediated via activation of Trk receptors, which therefore appear to remain crucial to plasticity of adult neurons. Our results indicate that m aturing neurons acquire protection against cell death, induced in the absen ce of neurotrophin, while retaining their growth responsiveness to these fa ctors. (C) 2001 John Wiley & Sons, Inc.