Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Department of Morphological Sciences, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Neurotox Res. 2017 Nov;32(4):585-593. doi: 10.1007/s12640-017-9767-0. Epub 2017 Jun 27.
In the present study, we investigate the effect of severe hyperhomocysteinemia on biochemical (creatine kinase activity), behavioral (memory tests), and histological assessments (hippocampal volume). A possible neuroprotective role of creatine on hyperhomocysteinemia effects was also evaluated. Severe hyperhomocysteinemia was induced in neonate rats (starting at 6 days of age) by treatment with homocysteine (0.3-0.6 μmol/g body weight) for 23 days. Creatine (50 mg/kg body weight) was administered concomitantly with homocysteine. Controls received saline in the same volumes. Twelve hours after the last injection, the rats were submitted to behavioral tests [(recognition task (NOR)] and inhibitory avoidance (IA)]. Following behavioral assessment, the animals were perfused and decapitated, the brain removed for subsequent morphological analysis of the hippocampus. Another group of animals was used to test creatine kinase activity in hippocampus. The results showed that rats treated with homocysteine decreased (44%) the exploration of the novel object in NOR. In the IA task, homocysteine-treated animals presented decreased latencies to step down the platform in short- (32%) and long-term (18%) testings (3 h and 7 days, respectively), evidencing aversive memory impairment. Hippocampal volume was not altered by homocysteine administration. Hyperhomocysteinemia decreased (45%) creatine kinase activity, and creatine was able to prevent such effect probably by creatine kinase/phosphocreatine/creatine homeostasis, which serves as energy circuit within of the cell. This finding may be associated, at least in part, with memory improvement, suggesting that creatine might represent an effective adjuvant to protect against the effects of high homocysteine plasma levels.
在本研究中，我们研究了严重高同型半胱氨酸血症对生化（肌酸激酶活性）、行为（记忆测试）和组织学评估（海马体积）的影响。还评估了肌酸对高同型半胱氨酸血症影响的可能神经保护作用。通过用同型半胱氨酸（0.3-0.6 μmol/g 体重）处理新生大鼠（从 6 天大开始）诱导严重高同型半胱氨酸血症，持续 23 天。同时给予肌酸（50 mg/kg 体重）。对照组给予相同体积的生理盐水。最后一次注射后 12 小时，大鼠进行行为测试[识别任务（NOR）]和抑制回避（IA）]。行为评估后，对动物进行灌注和断头，取出大脑进行海马形态学分析。另一组动物用于测试海马中的肌酸激酶活性。结果表明，用同型半胱氨酸处理的大鼠在 NOR 中减少了（44%）对新物体的探索。在 IA 任务中，同型半胱氨酸处理的动物在短时间（32%）和长时间（18%）测试（分别为 3 小时和 7 天）中减少了跳下平台的潜伏期，表明记忆受损。海马体积不受同型半胱氨酸给药的影响。高同型半胱氨酸血症降低（45%）肌酸激酶活性，肌酸能够通过肌酸激酶/磷酸肌酸/肌酸稳态来预防这种作用，该稳态作为细胞内的能量回路。这一发现可能至少部分与记忆改善有关，表明肌酸可能是一种有效的辅助手段，可预防高同型半胱氨酸血症的影响。
