TRIIODOTHYRONINE EXERTS A TROPHIC ACTION ON RAT SENSORY NEURON SURVIVAL AND NEURITE OUTGROWTH THROUGH DIFFERENT PATHWAYS

Apart from several growth factors which play a crucial role in the sur vival and development of the central and peripheral nervous systems, t hyroid hormones can affect different processes involved in the differe ntiation and maturation of neurons. The present study was initiated to determine whether triiodothyronine (T-3) affects the survival and neu rite outgrowth of primary sensory neurons in vitro. Dorsal root gangli a (DRG) from 19-day-old embryos or newborn rats were plated in explant or dissociated cell cultures. The effect of T-3 On neuron survival wa s tested, either in mixed DRG cell cultures, where neurons grow with n on-neuronal cells, or in neuron-enriched cultures where non-neuronal c ells were eliminated at the outset. T-3, in physiological concentratio ns, promoted the growth of neurons in mixed DRG cell cultures as well as in neuron-enriched cultures without added nerve growth factor (NGF) . Since neuron survival in neuron-enriched cultures cannot be promoted by endogenous neurotrophic factors synthesized by non-neuronal cells, the increased number of surviving neurons was due to a direct trophic action of T-3 Another trophic effect was revealed in this study: Tg s ustained the neurite outgrowth of sensory neurons in DRG explants. The stimulatory effect of T-3 on nerve fibre outgrowth was considerably r educed when non-neuronal cell proliferation was inhibited by the antim itotic agent cytosine arabinoside, and was completely suppressed when the great majority of non-neuronal cells were eliminated in neuron-enr iched cultures. These results indicate that the stimulatory effect of T-3 On neurite outgrowth is mediated through non-neuronal cells. It is conceivable that T-3 up-regulates Schwann cell expression of a neurot rophic factor, which in turn stimulates axon growth of sensory neurons . Together, these results demonstrate that T-3 promotes both survival and neurite outgrowth of primary sensory neurons in DRG cell cultures. The trophic actions of T-3 On neuron survival and neurite outgrowth o perate under two different pathways.