Graduation Program in Pharmacology, Center of Health Sciences (CCS), Federal University of Santa Maria, Santa Maria, RS, CEP 97105-900, Brazil.
Neurochem Res. 2013 Aug;38(8):1704-14. doi: 10.1007/s11064-013-1072-6. Epub 2013 May 16.
Piracetam improves cognitive function in animals and in human beings, but its mechanism of action is still not completely known. In the present study, we investigated whether enzymes involved in extracellular adenine nucleotide metabolism, adenosine triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase and adenosine deaminase (ADA) are affected by piracetam in the hippocampus and cerebral cortex of animals subjected to scopolamine-induced memory impairment. Piracetam (0.02 μmol/5 μL, intracerebroventricular, 60 min pre-training) prevented memory impairment induced by scopolamine (1 mg/kg, intraperitoneal, immediately post-training) in the inhibitory avoidance learning and in the object recognition task. Scopolamine reduced the activity of NTPDase in hippocampus (53 % for ATP and 53 % for ADP hydrolysis) and cerebral cortex (28 % for ATP hydrolysis). Scopolamine also decreased the activity of 5'-nucleotidase (43 %) and ADA (91 %) in hippocampus. The same effect was observed in the cerebral cortex for 5'-nucleotidase (38 %) and ADA (68 %) activities. Piracetam fully prevented scopolamine-induced memory impairment and decrease of NTPDase, 5'-nucleotidase and adenosine deaminase activities in synaptosomes from cerebral cortex and hippocampus. In vitro experiments show that piracetam and scopolamine did not alter enzymatic activity in cerebral cortex synaptosomes. Moreover, piracetam prevented scopolamine-induced increase of TBARS levels in hippocampus and cerebral cortex. These results suggest that piracetam-induced improvement of memory is associated with protection against oxidative stress and maintenance of NTPDase, 5'-nucleotidase and ADA activities, and suggest the purinergic system as a putative target of piracetam.
吡拉西坦可改善动物和人类的认知功能，但作用机制尚不完全清楚。在本研究中，我们研究了是否参与细胞外腺嘌呤核苷酸代谢的酶，三磷酸二酯酶（NTPDase）、5'-核苷酸酶和腺苷脱氨酶（ADA），在被东莨菪碱诱导记忆障碍的动物的海马体和大脑皮层中受到吡拉西坦的影响。吡拉西坦（0.02 μmol/5 μL，脑室内，训练前 60 分钟）可防止东莨菪碱（1 mg/kg，腹腔内，立即训练后）引起的抑制性回避学习和物体识别任务中的记忆障碍。东莨菪碱降低了海马体中 NTPDase 的活性（ATP 和 ADP 水解的 53%）和大脑皮层（ATP 水解的 28%）。东莨菪碱还降低了 5'-核苷酸酶（43%）和 ADA（91%）在海马体中的活性。在大脑皮层中观察到相同的效果，5'-核苷酸酶（38%）和 ADA（68%）的活性。吡拉西坦完全防止了东莨菪碱诱导的记忆障碍和大脑皮层和海马体突触体中 NTPDase、5'-核苷酸酶和腺苷脱氨酶活性的降低。体外实验表明，吡拉西坦和东莨菪碱不会改变大脑皮层突触体中的酶活性。此外，吡拉西坦可防止东莨菪碱诱导的海马体和大脑皮层中 TBARS 水平升高。这些结果表明，吡拉西坦诱导的记忆改善与抗氧化应激的保护和 NTPDase、5'-核苷酸酶和 ADA 活性的维持有关，并提示嘌呤能系统可能是吡拉西坦的作用靶点。
