Maintenance of noradrenergic sympathetic innervation in the involuted thymus of the aged Fischer 344 rat

Abstract

Sympathetic postganglionic noradrenergic (NA) fibers innervate both primary and secondary lymphoid organs in the rat. In secondary lymphoid organs such as the spleen and lymph nodes, this innervation diminishes with age. This study was undertaken to determine whether a similar decline in NA innervation occurs in the thymus. Thymuses from Fischer 344 (F344) rats were examined at 3, 8, 12, 17, 21, and 27 months of age with fluorescence histochemistry for catecholamines, and with high-performance liquid chromatography with electrochemical detection (LCEC) for quantitation of monoamines. In adult animals of all age groups, the compartmentation of NA innervation was maintained; NA fibers entered the thymus with the vasculature and arborized in the cortex, particularly in the subcapsular region and around the vasculature at the corticomedullary junction. NA nerve fibers were sparse in the thymuses from 3-month-old rats and increased in density at 8 and 12 months of age. The density of NA nerve fibers in the thymuses from 17, 21, and 27 months of age increased further, in parallel with thymic involution. Quantitation of monoamines revealed stable thymic norepinephrine (NE) and 5-hydroxytryptamine (5-HT) content from 8 to 27 months of age. The lower levels of NE detected at 3 months of age may reflect a slow maturation and reorganization of this fiber system as a developmental phenomenon. Measurement of 3-methoxy-4-hydroxy-phenyleneglycol (MHPG), a major metabolite of NE, showed a more than twofold rise from 3 to 12 months of age, and remained high through 27 months of age. The resultant MHPG NE ratios, as an index of NE availability for interaction with target cells, showed a decline from 3 months of age through 17–21 months of age, followed by a marked rise at 27 months of age. These findings suggest that the thymus is able to maintain NA innervation in the face of involution, and that these fibers provide a NA-enriched microenvironment for interaction with adrenergic receptors on thymocytes.