INFLUENCE OF LONG-TERM TREATMENT WITH L-DEPRENYL ON THE AGE-DEPENDENTCHANGES IN RAT-BRAIN MICROANATOMY

The present study was designed to assess whether treatment with the mo noamine oxidase-B (MAO-B) inhibitor L-deprenyl, which has been documen ted to increase both mean and maximum survival in aged rats as well as sexual performance and cognitive function, has any effect on the age- related microanatomical changes occurring in the rat brain. Male Sprag ue-Dawley rats received a subcutaneous injection of 0.25 mg/kg L-depre nyl every other day from the 19th to the 24th month of age. Age-matche d control rats were injected with saline, whereas 11-month-old untreat ed rats were used as an adult reference group. Both body and brain wei ght were increased as a function of age, and they were unaffected by t reatment with L-deprenyl. The density of nerve cell profiles in the fr ontal cortex, in the CA-1 and CA-3 subfields of the hippocampus, in th e dentate gyrus and in the cerebellar cortex were decreased in aged ra ts in comparison with adult rats. The density of nerve cell profiles i n the above brain areas of L-deprenyl-treated rats was not significant ly higher in comparison with age-matched control animals with the exce ption of Purkinje neuron profiles. The intensity of Nissl's staining, which may be related to the protein synthetic capabilities of nerve ce lls, is reduced within pyramidal neurons of the hippocampus and Purkin je neurons of the cerebellar cortex of aged rats. The intensity of Nis sl's staining in L-deprenyl-treated rats was not different from adult rats, Lipofuscin deposition was significantly increased within the cyt oplasm of pyramidal neurons of the frontal cortex, of the CA-3 subfiel d of the hippocampus and of Purkinje neurons of the cerebellar cortex. L-Deprenyl administration decreased lipofuscin accumulation within th e cytoplasm of the above mentioned nerve cell types. The density of su lphide-silver staining in the intrahippocampal pathway of mossy fibres . which participate in the elaboration of passive avoidance responses, is decreased in aged rats. Treatment with L-deprenyl counters this ag e-related reduction. The above results suggest that long-term treatmen t with L-deprenyl is able to counter the expression of some microanato mical changes typical of aging brain.