ENDOGENOUS NEUROTROPHIN-3 SUPPORTS THE SURVIVAL OF A SUBPOPULATION OFSENSORY NEURONS IN NEONATAL RAT

Neurotrophin-3 promotes the differentiation and supports the survival of neuroblasts derived from the neural crest in early development. Neu rotrophin-3 also plays an important role in the differentiation and su rvival of a subpopulation of large sensory neurons after their axons a rrive at their targets. Proprioception and mechanoception are lost aft er gene deletion of neurotrophin-3 or its high-affinity receptor, TrkC . However, the function of neurotrophin-3 during late development and in mature animals is not clear. We have used an antiserum, specific fo r neurotrophin-3, to neutralize endogenous neurotrophin-3 in postnatal rats to determine its role in late sensory neuron development. Admini stration of the antiserum for a period of two weeks, but not one week, resulted in a 20% reduction in the number of primary sensory neurons in the dorsal root ganglia and a 19% reduction in the number of myelin ated axons in the saphenous nerve. The size distribution histogram als o indicated that a subpopulation of large neurons was lost by the neur otrophin-3 antiserum treatment. This neuronal loss was accompanied by reduced cell soma sizes and weights of the ganglia. Immunoreactivities for calbindin and calretinin were reduced in the trigeminal and dorsa l root ganglia and nerve fibres surrounding whisker hair follicles. Th e number of Merkel cells in touch domes labelled with quinacrine and t he number of parvalbumin-immunoreactive neurons in the dorsal root gan glia were significantly reduced by the antibody treatment. In contrast , the number of muscle spindles in the gastrocnemius muscle is not red uced by the neurotrophin-3 antiserum. Together, these results indicate that a subpopulation of primary sensory neurons in the neonatal rat r equires neurotrophin-3 for their survival and expression of calcium bi nding proteins. In addition, Merkel cells in touch domes also require neurotrophin-3 for their survival. Thus, endogenous neurotrophin-3 in neonatal rats is critical for the survival and function of a subpopula tion of primary sensory neurons and Merkel cells. (C) 1998 IBRO. Publi shed by Elsevier Science Ltd.