Paul Vanaja, Reddy Leema, Ekambaram P
Department of Pharmacology and Environmental Toxicology, Dr. A.L.M. Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai 600 113.
Indian J Physiol Pharmacol. 2005 Apr;49(2):179-86.
In the present study, memory formation to an acquired pole-climbing shock avoidance task was tested in young adult (3-4 month-old) and aged (24-25 month-old) rats. The data were correlated with the activity of nitric oxide synthase (NOS) and the concentration of nitric oxide (NO) in the hippocampus, midbrain, cortex and cerebellum. Motor co-ordination was tested in both groups. Memory test and NO determination were carried out in another set of young and aged groups, 15 min after intraperitoneal administration of NO precursor, L-arginine (500, 1000 mg/kg) or NO donor, sodium nitroprusside (SNP) (1.25, 2.5 mg/kg). No difference was found between the motor co-ordination performances of young and aged animals. But the aged animals were not able to perform the shock avoidance pole-climbing task as readily as the young animals. It is suggestive of an impairment of memory formation of the acquired task in the aged animals. The synthesis of NO which is known to regulate memory process in the hippocampus, was lower in this brain region of aged animals as compared to that in young animals. L-arginine (1000 mg/kg) and SNP (2.5 mg/kg) increased the concentration of NO in the hippocampus and shortened the time of pole-climbing shock avoidance task in young as well as in aged animals. These results lead to a conclusion that a decreased synthesis of NO in the hippocampus in responsible for an impairment of memory formation in aged animals and that an increase in the concentration of NO in the hippocampus by L-arginine (1000 mg/kg) or SNP (2.5 mg/kg) results in a promotion of memory formation in the young adult rats and a reversal of memory deterioration in the aged animals. Thus, NO precursor and NO donor may be effective in reverting cognitive dysfunction associated with Alzheimer's disease, an ageing-induced neurodegenerative disease.
在本研究中，对年轻成年（3 - 4月龄）和老年（24 - 25月龄）大鼠进行了后天性爬杆躲避电击任务的记忆形成测试。数据与海马体、中脑、皮层和小脑中一氧化氮合酶（NOS）的活性以及一氧化氮（NO）的浓度相关。对两组大鼠的运动协调性进行了测试。在另一组年轻和老年大鼠中，腹腔注射NO前体L - 精氨酸（500、1000 mg/kg）或NO供体硝普钠（SNP）（1.25、2.5 mg/kg）15分钟后，进行记忆测试和NO测定。年轻和老年动物的运动协调能力没有差异。但老年动物不像年轻动物那样容易完成躲避电击的爬杆任务。这表明老年动物后天性任务的记忆形成受损。已知在海马体中调节记忆过程的NO合成，在老年动物的这个脑区比年轻动物低。L - 精氨酸（1000 mg/kg）和SNP（2.5 mg/kg）增加了海马体中NO的浓度，并缩短了年轻和老年动物完成爬杆躲避电击任务的时间。这些结果得出一个结论，即海马体中NO合成减少是老年动物记忆形成受损的原因，而L - 精氨酸（1000 mg/kg）或SNP（2.5 mg/kg）使海马体中NO浓度增加，导致年轻成年大鼠记忆形成得到促进，老年动物记忆衰退得到逆转。因此，NO前体和NO供体可能有效逆转与阿尔茨海默病（一种衰老引起的神经退行性疾病）相关的认知功能障碍。
