Preethi Jayakumar, Singh Hemant K, Rajan Koilmani E
Behavioral Neuroscience Laboratory, Department of Animal Science, School of Life Sciences, Bharathidasan University Tiruchirappalli, India.
Laboratories for CNS Disorder, Learning and Memory, Division of Pharmacology, Central Drug Research Institute Lucknow, India.
Front Pharmacol. 2016 Jun 27;7:166. doi: 10.3389/fphar.2016.00166. eCollection 2016.
Bacopa monniera extract (CDRI-08; BME) has been known to improve learning and memory, and understanding the molecular mechanisms may help to know its specificity. We investigated whether the BME treatment alters the methylation status of reelin and brain-derived neurotropic factor (BDNF) to enhance the memory through the interaction of N-methyl-D-aspartate receptor (NMDAR) with synaptic proteins. Rat pups were subjected to novel object recognition test following daily oral administration of BME (80 mg/kg) in 0.5% gum acacia (per-orally, p.o.; PND 15-29)/three doses of 5-azacytidine (5-azaC; 3.2 mg/kg) in 0.9% saline (intraperitoneally, i.p.) on PND-30. After the behavioral test, methylation status of reelin, BDNF and activation of NMDAR, and its interactions with synaptic proteins were tested. Rat pups treated with BME/5-azaC showed higher discrimination towards novel objects than with old objects during testing. Further, we observed an elevated level of unmethylated DNA in reelin and BDNF promoter region. Up-regulated reelin along with the splice variant of apolipoprotein E receptor 2 (ApoER 2, ex 19) form a cluster and activate NMDAR through disabled adopter protein-1 (DAB1) to enhance BDNF. Observed results suggest that BME regulate reelin epigenetically, which might enhance NMDAR interactions with synaptic proteins and induction of BDNF. These changes may be linked with improved novel object recognition memory.
已知假马齿苋提取物（CDRI - 08；BME）可改善学习和记忆，了解其分子机制可能有助于知晓其特异性。我们研究了BME处理是否会改变Reelin和脑源性神经营养因子（BDNF）的甲基化状态，以通过N - 甲基 - D - 天冬氨酸受体（NMDAR）与突触蛋白的相互作用来增强记忆。在出生后第15 - 29天，给幼鼠每日经口灌胃给予BME（80 mg/kg，溶于0.5%阿拉伯胶中）；在出生后第30天，给幼鼠腹腔注射三剂5 - 氮杂胞苷（5 - azaC；3.2 mg/kg，溶于0.9%盐水中）。行为测试后，检测Reelin、BDNF的甲基化状态以及NMDAR的激活情况及其与突触蛋白的相互作用。用BME/5 - azaC处理的幼鼠在测试期间对新物体的辨别能力高于对旧物体的辨别能力。此外，我们观察到Reelin和BDNF启动子区域未甲基化DNA水平升高。上调的Reelin与载脂蛋白E受体2（ApoER 2，外显子19）的剪接变体形成簇，并通过失能衔接蛋白-1（DAB1）激活NMDAR以增强BDNF。观察结果表明，BME通过表观遗传方式调节Reelin，这可能增强NMDAR与突触蛋白的相互作用并诱导BDNF的产生。这些变化可能与改善新物体识别记忆有关。
