VACUOLAR NEURITIC DYSTROPHY IN AGED MOUSE SUPERIOR CERVICAL SYMPATHETIC-GANGLIA IS STRAIN-SPECIFIC

We have developed a model of autonomic nervous system aging using the mouse superior cervical sympathetic ganglion (SCG) which is characteri zed by the reproducible development of distinctive, markedly-enlarged neuritic swellings (vacuolar neuritic dystrophy, VND), These structure s contained an admixture of lucent vacuoles and subcellular organelles , and involved both presynaptic and postsynaptic ganglionic elements. Quantitation of the frequency of VND was accomplished at the light mic roscopic level and validated by ultrastructural examination. VND lesio ns were 30-100-fold more frequent in the aged mouse paravertebral SCG than in the prevertebral celiac/superior mesenteric (C/SMG) sympatheti c ganglia. Although VND was identified in all ages of mice examined, t he number of lesions increased significantly with age. The frequency o f VND was a function of the strain of mouse examined with a 40-fold di fference in VND frequency between C57BL6 mice, the least involved stra in, and the DBA/2J strain, which was most affected and began to develo p significant numbers of lesions at an early age. As in our human stud ies of aging in the sympathetic nervous system, there was a prominent gender effect with males developing twofold greater numbers of VND les ions than females. Mice maintained on a significant calorie restricted diet for 30 months developed 70% fewer lesions than ad libitum-fed, a ge and sex matched controls. The aging mouse SCG, therefore, represent s a robust animal model with reproducible, quantifiable and unambiguou s neuropathology. Insights into pathogenetic mechanisms gained in the subsequent analysis of this relatively simple peripheral sympathetic n ervous system model may contribute to the understanding of some of the most complex and significant problems involving higher brain function . (C) 1998 Elsevier Science B.V. All rights reserved.