INFLUENCE OF TREATMENT WITH L-DEPRENYL ON THE STRUCTURE OF THE CEREBELLAR CORTEX OF AGED RATS

Treatment with L-deprenyl increases mean and maximum life span in the rat and reverses memory and learning deficits associated with old age. Since only sparse information is available concerning the influence o f L-deprenyl administration on the aging brain microanatomy, we have i nvestigated the effect of long-term treatment with L-deprenyl on the s tructure of the cerebellar cortex in the aged rat. The cerebellar cort ex was used since it represents a useful model for assessing age-relat ed changes in nervous system anatomy and function. Male Sprague-Dawley rats were treated from the 19th to the 24th month of age with a daily oral dose of 1.25 mg/kg or 5 mg/kg L-deprenyl. Age-matched rats were left untreated and used as a control group. Eleven-month-old untreated rats were used as an adult reference group. The density of Purkinje a nd granule neuron profiles as well as the intensity of Nissl's stainin g within the cytoplasm of Purkinje neurons were reduced in 24-month in comparison with 11-month rats. Moreover, an increased accumulation of lipofuscin was noticeable in the cytoplasm of Purkinje neurons of old rats as well as an increase in MAO-B activity in the molecular layer of the cerebellar cortex. The two doses of L-deprenyl increased the de nsity of both Purkinje and granule neuron profiles and the intensity o f Nissl's staining in the cytoplasm of Purkinje neurons and reduced li pofuscin deposition within Purkinje neurons. The lower dose of L-depre nyl caused only a slight decrease in MAO-B activity, whereas the 5-mg/ kg/day dose remarkably reduced it. These results suggest that long-ter m treatment with L-deprenyl counters the expression of some age-relate d microanatomical changes in the rat cerebellar cortex. The possible i ndependence of the effects of the compound on age-related microanatomi cal changes of the cerebellar cortex and on MAO-B inhibitory activity is discussed.