EFFECT OF LONG-TERM TREATMENT WITH L-DEPRENYL ON THE AGE-DEPENDENT MICROANATOMICAL CHANGES IN THE RAT HIPPOCAMPUS

Chronic treatment with L-deprenyl increases both mean and maximum life span and improves cognitive functions in the aged rat. The present st udy was designed to evaluate whether long-term treatment with L-depren yl at a dosage not inhibiting the monoamine oxidase-B (MAO-B) (1.25 mg /kg/day) or inhibiting the enzyme activity (5 mg/kg/day) had any effec t on the age-dependent microanatomical changes in the rat hippocampus. The hippocampus was chosen in view of its key role in learning and me mory functions. Treatment with L-deprenyl started at 19 months and las ted until the 24th month of age. Age-matched untreated rats were used as a control, whereas 11-month-old rats were used as an adult referenc e group. The number of nerve cell and glial fibrillary acidic protein- immunoreactive astrocyte profiles in the CA(1) and CA(3) fields of the hippocampus and in the dentate gyrus was decreased and increased, res pectively in aged compared with adult rats. Treatment with 5 mg/kg/day , but not with 1.25 mg/kg/day L-deprenyl increased the number of neuro nal profiles and decreased the number of astrocytes in the hippocampus of aged rats. The density of zinc stores in the associative intrahipp ocampal pathway of messy fibres, which was decreased in aged animals, was increased after treatment with the two doses of L-deprenyl. Lipofu scin accumulation within the cytoplasm of pyramidal neurons of the hip pocampus was reduced dose dependently by L-deprenyl treatment. These r esults suggest that long-term treatment with L-deprenyl is able to cou nter the expression of age-dependent microanatomical changes in the ra t hippocampus. These effects seem only partially correlated with the M AO-B inhibitory activity of L-deprenyl.