Pathologic alterations in pre- and postsynaptic elements in aged mouse sympathetic ganglia

Dysfunction of the sympathetic autonomic nervous system is an increasingly recognized, although poorly understood, complication of increasing 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 ultrastructural appearance of perikarya, dendritic processes, preterminal axons, and synapses in selected sympathetic ganglia as well as the three-dimensional structure of the dendritic arborizations of principal sympathetic neurons using intracellular injections of Lucifer Yellow. Ultrastructural examination demonstrated numerous markedly enlarged presynaptic terminal axons and synapses which distorted the contours of perikarya and dendrites of neurons within the prevertebral celiac/superior mesenteric and paravertebral superior cervical and stellate sympathetic ganglia of aged mice. Dilated preterminal axons had the distinctive ultrastructural appearance of neuroaxonal dystrophy, a pathologic process described in a wide variety of clinical and experimental entities. Dystrophic axons were identical in ultrastructural appearance in young and old animals, differing only in frequency. A distinctive type of ultrastructural alteration, characterized by markedly distended neurites containing numerous vacuoles, was confined to the superior cervical ganglia and also increased in frequency with aging. Although many intraganglionic vacuolated processes disappeared with surgical interruption of the cervical sympathetic trunk, which contains the preganglionic axons innervating the superior cervical ganglia, others persisted. In addition, the presence in some processes of admixed ribosomes, lipofuscin, or continuity with the cell body indicated that numerous neuritic alterations within aged sympathetic ganglia were likely of dendritic origin. Intracellular injections of Lucifer Yellow into principal 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 superior cervical ganglia. Sympathetic neurons of aged superior cervical ganglia, but not superior mesenteric ganglia, appeared significantly smaller with regard to total dendritic length, extent, and branching when compared to those of young animals. In the aged superior cervical ganglia, short, stunted dendritic processes also exhibited large, focal, often multiple, swellings, a phenomenon infrequently observed in the superior cervical ganglia of young animals. The celiac/ superior mesenteric ganglia of aged or young adult mouse failed to exhibit comparable dendritic swellings. These observations may provide a neuropathological basis for understanding age-related changes in autonomic function observed in animals and man, and provide a model system in which age-related pathogenetic mechanisms resulting in neuroaxonal dystrophy and dendritic alterations can be studied.