Zugno Alexandra I, Pereira Lenir O, Mattos Cristiane, Scherer Emilene B S, Netto Carlos A, Wyse Angela T S
Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil.
Metab Brain Dis. 2008 Jun;23(2):189-98. doi: 10.1007/s11011-008-9085-6. Epub 2008 Apr 24.
Guanidinoacetate methyltransferase deficiency (GAMT-deficiency) is an inborn error of metabolism biochemically characterized by accumulation of guanidinoacetate (GAA) and depletion of creatine; the pathogenesis of brain dysfunction in this disorder is not yet established. In the present study we investigated the effect of intrastriatal administration of GAA on acetylcholinesterase (AChE) activity and on memory acquisition, consolidation and retrieval of step-down inhibitory avoidance task in rat. Results showed that GAA significantly increased AChE activity in rat striatum 30 min (50%) and 3 h (25%), but not 6 h after drug administration. GAA impaired test session performance when applied 30 min before training or after training, and before testing sessions, i.e., impaired memory acquisition, consolidation and retrieval. When injected with a 6 hour interval, GAA affected only memory retrieval. Although the mechanisms of action of GAA on AChE activity and on memory are unclear, these findings suggest that the accumulation of GAA found in patients with GAMT-deficiency may be one of the mechanisms involved in neural dysfunction. Further studies are necessary to evaluate these mechanisms.
胍基乙酸甲基转移酶缺乏症（GAMT缺乏症）是一种先天性代谢紊乱，其生化特征是胍基乙酸（GAA）积累和肌酸耗竭；这种疾病中脑功能障碍的发病机制尚未明确。在本研究中，我们研究了纹状体内注射GAA对大鼠乙酰胆碱酯酶（AChE）活性以及对大鼠记忆获得、巩固和对递减式抑制回避任务的提取的影响。结果显示，给药30分钟（50%）和3小时（25%）后，GAA显著增加大鼠纹状体中的AChE活性，但给药6小时后未增加。在训练前30分钟或训练后以及测试前给药时，GAA损害测试阶段的表现，即损害记忆获得、巩固和提取。当间隔6小时注射时，GAA仅影响记忆提取。尽管GAA对AChE活性和记忆的作用机制尚不清楚，但这些发现表明，GAMT缺乏症患者中发现的GAA积累可能是神经功能障碍所涉及的机制之一。有必要进行进一步研究以评估这些机制。
