Hashemi Paria, Moloudi Mohammad Raman, Rahmani Helia, Hassanzadeh Katayoun, Vahabzadeh Zakaria, Izadpanah Esmael
Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Neurosciences Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Neurochem Res. 2025 Apr 16;50(3):144. doi: 10.1007/s11064-025-04393-z.
Memory impairment is one of the cognitive symptoms in Huntington's disease (HD) which appears before motor dysfunction in patients. Various molecular mechanisms, including disruptions in neurotrophins levels, are involved in the occurrence of memory problems in HD. Alpha-pinene (APN), a member of the monoterpene family, exhibited beneficial effects in animal models of neurodegenerative disorders. As a result, this study assessed the impact of APN on memory in the 3-nitropropionic acid (3-NP) induced model of HD in rats. Male Wistar rats received saline, 3-NP to model HD, or APN (1, 5, or 10 mg/kg) plus 3-NP for 21 days to assess APN's effects. Working and spatial memory were examined by the Y-maze and Morris-water-maze (MWM) tests. The mRNA levels of neurotrophins and their receptors in the brain cortex and hippocampus of the rats were quantitatively assessed through Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) analysis. The results showed that APN, at all three doses, significantly prevented the disease phenotype induced by 3-NP administration. In addition, APN treatment elevated the gene expression levels of BDNF, TrkA, TrkB, and CREB, while significantly decreasing P75 NTR showing a dose-dependent effect in the brain cortex and hippocampus, compared to the 3-NP group. These findings suggest that APN alleviates 3-NP-induced memory deficits by enhancing neurotrophins and their receptor levels in an animal model of HD.
记忆障碍是亨廷顿舞蹈症（HD）的认知症状之一，在患者出现运动功能障碍之前就会出现。包括神经营养因子水平紊乱在内的各种分子机制都与HD患者记忆问题的发生有关。α-蒎烯（APN）是单萜家族的一员，在神经退行性疾病的动物模型中显示出有益作用。因此，本研究评估了APN对3-硝基丙酸（3-NP）诱导的大鼠HD模型记忆的影响。雄性Wistar大鼠接受生理盐水、用于模拟HD的3-NP或APN（1、5或10mg/kg）加3-NP处理21天，以评估APN的作用。通过Y迷宫和莫里斯水迷宫（MWM）试验检测工作记忆和空间记忆。通过逆转录定量聚合酶链反应（RT-qPCR）分析定量评估大鼠大脑皮层和海马中神经营养因子及其受体的mRNA水平。结果表明，所有三个剂量的APN均显著预防了3-NP给药诱导的疾病表型。此外，与3-NP组相比，APN治疗提高了BDNF、TrkA、TrkB和CREB的基因表达水平，同时显著降低了大脑皮层和海马中P75 NTR的表达，呈现出剂量依赖性效应。这些发现表明，在HD动物模型中，APN通过提高神经营养因子及其受体水平来减轻3-NP诱导的记忆缺陷。
