RAT MATURE SYMPATHETIC NEURONS DERIVE NEUROTROPHIN-3 FROM PERIPHERAL EFFECTOR TISSUES

In a previous study we have demonstrated that endogenous neurotrophin 3 (NT3) is required for the survival of most sympathetic neurones in p ostnatal rats. However, the mechanisms underlying the action of NT3 on sympathetic neurones is not known. Neither is it understood whether N T3 is retrogradely transported from peripheral tissues or acts locally in an autocrine fashion. In the present study, NT3-mRNA was quantifie d in sympathetic effector tissues and NT3 protein was localized in int act and lesioned sympathetic nerves in rats. NT3-mRNA is expressed and developmentally regulated in many effector tissues including mesenter ic arteries, salivary gland, heart and kidney but hardly detectable in the superior cervical ganglia of adult animals. The majority of sympa thetic neurones express immunoreactivity for TrkA and TrkC in both neo natal and adult rats. Sympathetic somata are normally immunoreactive f or NT3, but the immunoreactivity is abolished by systemic administrati on of NT3 antibodies or axotomy of postganglionic neurones, suggesting an accumulation of NT3 from extraneuronal sources. Furthermore, the d etection of NT3-immunoreactivity in the internal carotid nerve as earl y as 3 h following a compression and only on the distal side indicates endogenous NT3 is retrogradely transported by sympathetic neurones. T hese studies provide evidence indicating that NT3, like nerve growth f actor, is an effector tissue-derived neurotrophic factor for sympathet ic neurones both during development and in the adult animal. Thus, we have provided a clear example that one type of neurone derives, throug h a retrograde transport mechanism, two neurotrophic factors simultane ously from its peripheral effector tissues.