PATHOLOGICAL ALTERATIONS IN PRESYNAPTIC AND POSTSYNAPTIC ELEMENTS IN AGED MOUSE SYMPATHETIC-GANGLIA

Dysfunction of the sympathetic autonomic nervous system is an increasi ngly recognized, although poorly understood, complication of increasin g age in experimental animals and man. In this study of young adult (4 -6 months old) and aged (12-24 months old) mice we have examined the u ltrastructural appearance of perikarya, dendritic processes, pretermin al axons, and synapses in selected sympathetic ganglia as well as the three-dimensional structure of the dendritic arborizations of principa l sympathetic neurons using intracellular injections of Lucifer Yellow . Ultrastructural examination demonstrated numerous markedly enlarged presynaptic terminal axons and synapses which distorted the contours o f perikarya and dendrites of neurons within the prevertebral celiac/su perior mesenteric and paravertebral superior cervical and stellate sym pathetic ganglia of aged mice. Dilated preterminal axons had the disti nctive ultrastructural appearance of neuroaxonal dystrophy, a patholog ic process described in a wide variety of clinical and experimental en tities. Dystrophic axons were identical in ultrastructural appearance in young and old animals, differing only in frequency. A distinctive t ype of ultrastructural alteration, characterized by markedly distended neurites containing numerous vacuoles, was confined to the superior c ervical ganglia and also increased in frequency with aging. Although m any intraganglionic vacuolated processes disappeared with surgical int erruption of the cervical sympathetic trunk, which contains the pregan glionic axons innervating the superior cervical ganglia, others persis ted. In addition, the presence in some processes of admired ribosomes, lipofuscin, or continuity with the cell body indicated that numerous neuritic alterations within aged sympathetic ganglia were Likely of de ndritic origin. Intracellular injections of Lucifer Yellow into princi pal sympathetic neurons demonstrated that the dendritic arborizations of the celiac/superior mesenteric ganglia neurons of young adult mice were significantly more complex and extensive than those of the superi or cervical ganglia. Sympathetic neurons of aged superior cervical gan glia, but not superior mesenteric ganglia, appeared significantly smal ler with regard to total dendritic length, extent, and branching when compared to those of young animals. In the aged superior cervical gang lia, short, stunted dendritic processes also exhibited large, focal, o ften multiple, swellings, a phenomenon infrequently observed in the su perior cervical ganglia of young animals. The celiac/superior mesenter ic ganglia of aged or young adult mouse failed to exhibit comparable d endritic swellings. These observations may provide a neuropathological basis for understanding age-related changes in autonomic function obs erved in animals and man, and provide a model system in which age-rela ted pathogenetic mechanisms resulting in neuroaxonal dystrophy and den dritic alterations can be studied.