Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-Anexo, Porto Alegre, RS, Brazil.
Neuroscience. 2009 Nov 10;163(4):1039-45. doi: 10.1016/j.neuroscience.2009.07.023. Epub 2009 Jul 18.
In the present study, we first investigated the effect of single homocysteine administration on consolidation of short- and long-term memories of inhibitory avoidance task in Wistar rats. We also measured brain-derived neurotrophic factor levels in the hippocampus and parietal cortex of rats. The influence of pretreatment with folic acid on behavioral and biochemical effects elicited by homocysteine was also studied. Wistar rats were subjected to a folic acid or saline pretreatment from their 22(nd) to 28(th) day of life; 12 h later they were submitted to a single administration of homocysteine or saline. For motor activity and memory evaluation we performed open-field and inhibitory avoidance tasks. Hippocampus and parietal cortex were obtained for brain-derived neurotrophic factor immunocontent determination. Results showed that homocysteine impaired short- and long-term memories and reduced brain-derived neurotrophic factor levels in the hippocampus. Pretreatment with folic acid prevented both the memory deficit and the reduction in the brain-derived neurotrophic factor immunocontent induced by homocysteine injection. Further studies are required to determine the entire mechanism by which folic acid acts and its potential therapeutic use for memory impairment prevention in homocystinuric patients.
在本研究中，我们首先研究了单一同型半胱氨酸给药对 Wistar 大鼠抑制性回避任务的短期和长期记忆巩固的影响。我们还测量了大鼠海马体和顶叶皮质中的脑源性神经营养因子水平。还研究了叶酸预处理对同型半胱氨酸引起的行为和生化效应的影响。Wistar 大鼠从第 22 天到第 28 天接受叶酸或生理盐水预处理；12 小时后，它们接受单次同型半胱氨酸或生理盐水给药。为了进行运动活动和记忆评估，我们进行了旷场和抑制性回避任务。获得海马体和顶叶皮质以测定脑源性神经营养因子免疫含量。结果表明，同型半胱氨酸损害了短期和长期记忆，并降低了海马体中的脑源性神经营养因子水平。叶酸预处理可预防同型半胱氨酸注射引起的记忆缺陷和脑源性神经营养因子免疫含量降低。需要进一步研究以确定叶酸作用的完整机制及其在预防同型胱氨酸尿症患者记忆障碍方面的潜在治疗用途。
