Adrenal medulla and substantia nigra co-grafts in peripheral nerve: chromaffin cells survive for long time periods and prevent degeneration of nigral neurons

Abstract

A series of degenerative cytoskeletal changes characterize grafts of embryonic substantia nigra when isolated for long time periods in the peripheral nervous system. This study was designed to determine whether the adrenal medulla could modulate the cytoskeletal changes in the substantia nigra when co-grafted within peripheral nerves. The sciatic nerves of young adult rats received single transplants of embryonic day 15 substantia nigra or co-transplants of substantia nigra plus young adult adrenal medulla in close proximity. Immunocytochemistry was used to examine the expression of tyrosine hydroxylase, phosphorylated (RT97) and non-phosphorylated (SMI-32) neurofilament proteins in the grafts. Single substantia nigra grafts, examined after 1 month, consisted of numerous neurons and fibers that expressed the epitope for tyrosine hydroxylase. Normal spatial distributions of the phosphorylated and non-phosphorylated neurofilament subunits were observed. In contrast, single 1-year-old nigral transplants were shrunken, contained significantly fewer tyrosine hydroxylase positive neurons and displayed abnormal neurofilament staining patterns including swollen axons, a reduction in the density of labeled axons and perikaryal accumulation of the phosphorylated neurofilament subunit. When co-grafted with the adrenal medulla, the nigral transplants did not show the degenerative cytoskeletal aspects evident in the single 1-year-old grafts. The loss of neurons was prevented and the neurofilament immunolabeling was indistinguishable from the young substantia nigra preparations. In addition, all the 1-year-old adrenal medulla grafts were viable within the peripheral nerves, consisting of hundreds of cells identified by immunoreactivity to tyrosine hydroxylase and the rat β-nerve growth factor receptor (192-IgG). The experiments illustrate a strong protective effect by the adrenal medulla on neurons of the substantia nigra in the peripheral nerve environment. It is suggested that a catecholaminergic trophic source and/or neural interactions with the adrenal medulla may be important factors in the long-term survival of neurons and maintenance of normal cytoskeletal characteristics in the grafted substantia nigra neurons under these experimental circumstances.