Thangaleela Subramanian, Shanmugapriya Vasudevan, Mukilan Murugan, Radhakrishnan Karuppasamy, Rajan Koilmani Emmanuvel
Behavioural Neuroscience Laboratory, Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli, India.
Department of Zoology, Government Arts College, Karur, India.
Ann Neurosci. 2018 Jul;25(2):90-97. doi: 10.1159/000486842. Epub 2018 Feb 2.
Earlier, we showed that nicotinamide (NAM) treatment impairs spatial memory through the downregulation of CREB-Sirt 1-brain-derived neurotrophic factor () signaling cascade.
In this study, we examine whether NAM treatment alters CREB-regulated genes through -microRNAs.
To test this hypothesis, goldfish () were divided into 2 groups: (i) vehicle group (VEH; double distilled water intra-peritoneally [i.p.]) (ii) nicotinamide group (NAM, 1,000 mg/kg, i.p.) and again divided into VEH untrained/trained, NAM untrained/trained. One hour after receiving VEH or NAM, individuals were subject to contextual fear conditioning (CFC) training. After 24 h, both the groups were tested for contextual fear memory. Subsequently, miR-132/212 levels, regulated immediate-early genes (IEGs: C-fos and EGR-1) and but not its receptor. -TrkB1were examined following 0' and 60' min after training, and compared with the untrained group.
We observed that NAM treatment significantly impaired fear memory. Further, the analysis showed that miR-132 level was not altered, but miR-212 level was significantly upregulated after CFC training only in NAM-treated fish. We also found that NAM treatment downregulated IEGs and but not its receptor TrkB1.
Present study suggests that NAM-treatment impaired fear memory and control IEGs, and TrkB1 expression by differentially regulating miR-132 and 212.
此前，我们发现烟酰胺（NAM）处理通过下调CREB-Sirt 1-脑源性神经营养因子（）信号级联反应损害空间记忆。
在本研究中，我们检测NAM处理是否通过-微小RNA改变CREB调节的基因。
为验证这一假设，将金鱼（）分为2组：（i）溶剂组（VEH；腹腔注射双蒸水[i.p.]）（ii）烟酰胺组（NAM，1000 mg/kg，i.p.），再分为VEH未训练/训练组、NAM未训练/训练组。接受VEH或NAM后1小时，对个体进行情境恐惧条件反射（CFC）训练。24小时后，对两组进行情境恐惧记忆测试。随后，在训练后0分钟和60分钟检测miR-132/212水平、调节即刻早期基因（IEGs：C-fos和EGR-1）以及，但不包括其受体-TrkB1，并与未训练组进行比较。
我们观察到NAM处理显著损害恐惧记忆。此外，分析表明，仅在接受NAM处理的金鱼中，CFC训练后miR-132水平未改变，但miR-212水平显著上调。我们还发现NAM处理下调了IEGs以及，但不包括其受体TrkB1。
本研究表明，NAM处理通过差异调节miR-132和212损害恐惧记忆并控制IEGs、和TrkB1的表达。
