TGF-BETA RESCUES TARGET-DEPRIVED PREGANGLIONIC SYMPATHETIC NEURONS INTHE SPINAL-CORD

Transforming growth factors beta (TGF-beta), a family of pleiotropic c ytokines, are widely distributed in the developing and adult nervous s ystem. in order to further determine the neural functions of TGF-beta, we have localized the TGF-beta isoforms 1, 2 and 3 in the adult rat a drenal medulla and studied the neuroprotective capacity of one represe ntative family member, TGF-beta 2, for those spinal cord neurons which innervate adrenal chromaffin cells and which die after destruction of the adrenal medulla. Unilateral electrothermal destruction of the adr enal medulla led to the disappearance of 25% of sympathetic preganglio nic neurons, which are located in the intermediolateral (IML) column o f thoracic spinal cord segments 7-10 and can be selectively marked by NADPH-diaphorase. The neurons which disappeared following adrenomedull ectomy constitute the full set of neurons that innervate the adrenal m edulla. Implantation of gelfoam soaked with 0.5 mu g TGF-beta 2 into t he adrenal wound cavity rescued all spinal cord neurons in the IML ips ilaterally to the lesioned side. Cytochrome c was not effective. Injec tions of [I-125]TGF-beta 2 into the adrenal medulla did not result in retrograde transport and subsequent labelling of spinal cord neurons, suggesting that TGF-beta may exert its neuroprotective actions by indi rect mechanisms. TGF-beta applied to cultured adrenocortical cells did not overtly increase the amount of mRNA for fibroblast growth factor- 2, an established trophic molecule for sympathetic preganglionic spina l cord neurons. The mechanisms by which TGF-beta exerts its neurotroph ic effect are therefore unclear. Even so, our data provide the first e vidence that TGF-beta may play an important role in vivo in the contro l of maintenance of a population of spinal cord neurons.