Havranek Tomas, Zatkova Martina, Lestanova Zuzana, Bacova Zuzana, Mravec Boris, Hodosy Julius, Strbak Vladimir, Bakos Jan
Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
J Neurosci Res. 2015 Jun;93(6):893-901. doi: 10.1002/jnr.23559. Epub 2015 Jan 22.
Brain oxytocin regulates a variety of social and affiliative behaviors and affects also learning and memory. However, mechanisms of its action at the level of neuronal circuits are not fully understood. The present study tests the hypothesis that molecular factors required for memory formation and synaptic plasticity, including brain-derived neurotrophic factor, neural growth factor, nestin, microtubule-associated protein 2 (MAP2), and synapsin I, are enhanced by central administration of oxytocin. We also investigated whether oxytocin enhances object recognition and acts as anxiolytic agent. Therefore, male Wistar rats were infused continuously with oxytocin (20 ng/µl) via an osmotic minipump into the lateral cerebral ventricle for 7 days; controls were infused with vehicle. The object recognition test, open field test, and elevated plus maze test were performed on the sixth, seventh, and eighth days from starting the infusion. No significant effects of oxytocin on anxious-like behavior were observed. The object recognition test showed that oxytocin-treated rats significantly preferred unknown objects. Oxytocin treatment significantly increased gene expression and protein levels of neurotrophins, MAP2, and synapsin I in the hippocampus. No changes were observed in nestin expression. Our results provide the first direct evidence implicating oxytocin as a regulator of brain plasticity at the level of changes of neuronal growth factors, cytoskeletal proteins, and behavior. The data support assumption that oxytocin is important for short-term hippocampus-dependent memory.
脑内催产素调节多种社会行为和亲和行为,同时也影响学习和记忆。然而,其在神经回路水平上的作用机制尚未完全明确。本研究检验了以下假设:通过向中枢给予催产素,可增强记忆形成和突触可塑性所需的分子因子,包括脑源性神经营养因子、神经生长因子、巢蛋白、微管相关蛋白2(MAP2)和突触素I。我们还研究了催产素是否能增强物体识别能力并发挥抗焦虑作用。因此,通过渗透微型泵连续7天将催产素(20 ng/µl)注入雄性Wistar大鼠的侧脑室;对照组注入溶剂。在开始注入后的第六、七、八天进行物体识别测试、旷场试验和高架十字迷宫试验。未观察到催产素对焦虑样行为有显著影响。物体识别测试表明,经催产素处理的大鼠显著偏好未知物体。催产素处理显著增加了海马体中神经营养因子、MAP2和突触素I的基因表达和蛋白质水平。巢蛋白表达未观察到变化。我们的结果提供了首个直接证据,表明催产素在神经元生长因子、细胞骨架蛋白和行为变化水平上是脑可塑性的调节因子。这些数据支持了催产素对短期海马体依赖性记忆很重要的假设。