Zeng Y C, Bongrani S, Bronzetti E, Cadel S, Ricci A, Valsecchi B, Amenta F
Sezione di Anatomia Umana, Università di Camerino, Italy.
Mech Ageing Dev. 1995 Apr 14;79(2-3):169-85. doi: 10.1016/0047-6374(94)01559-5.
Chronic treatment with L-deprenyl increases both mean and maximum life span and improves cognitive functions in the aged rat. The present study was designed to evaluate whether long-term treatment with L-deprenyl 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 effect on the age-dependent microanatomical changes in the rat hippocampus. The hippocampus was chosen in view of its key role in learning and memory functions. Treatment with L-deprenyl started at 19 months and lasted 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 reference group. The number of nerve cell and glial fibrillary acidic protein-immunoreactive astrocyte profiles in the CA1 and CA3 fields of the hippocampus and in the dentate gyrus was decreased and increased, respectively 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 neuronal profiles and decreased the number of astrocytes in the hippocampus of aged rats. The density of zinc stores in the associative intrahippocampal pathway of mossy fibres, which was decreased in aged animals, was increased after treatment with the two doses of L-deprenyl. Lipofuscin accumulation within the cytoplasm of pyramidal neurons of the hippocampus was reduced dose dependently by L-deprenyl treatment. These results suggest that long-term treatment with L-deprenyl is able to counter the expression of age-dependent microanatomical changes in the rat hippocampus. These effects seem only partially correlated with the MAO-B inhibitory activity of L-deprenyl.
长期使用L-司来吉兰治疗可增加老年大鼠的平均寿命和最长寿命，并改善其认知功能。本研究旨在评估以不抑制单胺氧化酶-B（MAO-B）的剂量（1.25毫克/千克/天）或抑制该酶活性的剂量（5毫克/千克/天）长期使用L-司来吉兰，是否会对大鼠海马体中与年龄相关的微观解剖学变化产生影响。鉴于海马体在学习和记忆功能中的关键作用，故选择其作为研究对象。L-司来吉兰治疗从19个月开始，持续至24个月龄。将年龄匹配的未治疗大鼠作为对照，而11个月大的大鼠作为成年参照组。与成年大鼠相比，老年大鼠海马体CA1和CA3区以及齿状回中神经细胞数量减少，而胶质纤维酸性蛋白免疫反应性星形胶质细胞数量增加。5毫克/千克/天剂量的L-司来吉兰治疗可增加老年大鼠海马体中的神经元数量并减少星形胶质细胞数量，但1.25毫克/千克/天剂量的治疗无此效果。老年动物海马体苔藓纤维联合海马内通路中锌储存密度降低，而两种剂量的L-司来吉兰治疗后该密度增加。L-司来吉兰治疗可剂量依赖性地减少海马体锥体细胞胞质内脂褐素的积累。这些结果表明，长期使用L-司来吉兰能够对抗大鼠海马体中与年龄相关的微观解剖学变化的表达。这些作用似乎仅部分与L-司来吉兰的MAO-B抑制活性相关。
