Department of Cardiothoracic Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu 210029, China; Divisions of Neurology and Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
Divisions of Neurology and Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
Neurosci Lett. 2014 Jun 6;570:97-101. doi: 10.1016/j.neulet.2014.04.018. Epub 2014 Apr 24.
Alpha 7 (α7) nicotinic acetylcholine receptor (α7-nAChR) is one of most high expressed nAChR subtypes in the brain. The activation of nAChRs enhances animal cognitive, learning and memory abilities. However, the role of genetic knockout (KO) of α7-nAChRs in animal cognition-associated behaviors is still obscure. An early report showed that α7-nAChR KO mice did not exhibit behavioral phenotypes, concerning the roles of α7-nAChRs in normal, cognition-associated behaviors. Later, α7-nAChR KO mice were found a deficit in animal spatial discrimination. The roles of α7-nAChRs in the alterations of hippocampal synaptic function during aging process are largely unknown. Here, we address this question by examining synaptic function using field potential recording in hippocampal slice preparations from adult (12-14 months old) and aged (22-24 months old) α7-nAChR KO and age-matched wild-type (WT) mice. We found that compared to aged WT mice, aged α7-nAChR KO mice exhibited significantly reduced size of evoked field synaptic potential and impaired long-term potentiation (LTP) in hippocampal CA3-CA1 synapses. However, adult α7-nAChR KO mice did not show a clear deficit in LTP although the basic synaptic transmission was also reduced compared to adult WT mice. In both age groups, there was no significant difference of paired-pulse facilitation between α7-nAChR KO and WT mice. Collectively, this study provides direct evidence, for the first time, that the impaired synaptic function occurs in aged α7-nAChR KO mice, suggesting an importance of α7-nAChRs in maintaining cognitive function during aging process.
α7 型烟碱型乙酰胆碱受体（α7-nAChR）是大脑中表达水平最高的烟碱型乙酰胆碱受体亚型之一。nAChR 的激活增强了动物的认知、学习和记忆能力。然而，α7-nAChR 基因敲除（KO）在与动物认知相关的行为中的作用仍不清楚。早期的报道表明，α7-nAChR KO 小鼠没有表现出行为表型，这涉及到 α7-nAChR 在正常认知相关行为中的作用。后来，α7-nAChR KO 小鼠在动物空间辨别中出现缺陷。α7-nAChR 在衰老过程中海马突触功能改变中的作用在很大程度上是未知的。在这里，我们通过在成年（12-14 个月大）和老年（22-24 个月大）α7-nAChR KO 和年龄匹配的野生型（WT）小鼠的海马脑片制备中使用场电位记录来研究突触功能，以解决这个问题。我们发现，与老年 WT 小鼠相比，老年 α7-nAChR KO 小鼠在海马 CA3-CA1 突触中诱发的场电位突触后电位幅度明显减小，长时程增强（LTP）受损。然而，与成年 WT 小鼠相比，成年 α7-nAChR KO 小鼠虽然基础突触传递也减少，但 LTP 没有明显缺陷。在两个年龄组中，α7-nAChR KO 和 WT 小鼠之间的成对脉冲易化没有显著差异。总之，这项研究首次提供了直接证据，表明在老年 α7-nAChR KO 小鼠中存在突触功能障碍，这表明 α7-nAChR 在衰老过程中维持认知功能的重要性。
