跑步锻炼对转基因痴呆小鼠海马改变作用的研究

Alzheimer's disease (AD) is a degenerative disease of the central nervous system with the characteristic of progressive cognitive dysfunction and memory impairment. The advanced features such as the cognition, learning and spatial memory abilities are closely related to hippocampal formation. For the first time in the world, our research team described the stereological methods to quantitatively investigate the three-dimensional changes of the myelinated fibers in brain. Using these methods, our team recently found that the total length of the myelinated fibers in the dentate gyrus of hippocampus was significantly decreased in the transgenic AD mouse that appeared to decline in the learning and spatial memory abilities. The brain has greater plasticity than we imagined. Some studies have found that running exercise might delay the progression of AD-related brain function decline. However, the neurobiological bases and the mechanism for the effects of exercise on AD brain function remain unclear. Therefore, in the current study, we will give exercise interventions to the transgenic AD mouse before and after the changes of learning and memory abilities. Then, we will combine behavioral methods, molecular biology techniques, stereological methods, electron microscope technique and immunofluorescence techniques to investigate the effects of running exercise on the learning and memory abilities, hippocampus structures and the related biological molecules in the different months of transgenic mouse model of AD. The results in the present study might be helpful for further understanding the effects of running exercise on cognitive and memory abilities of AD and recognizing the structural and molecular bases of these effects. The current study might be able to provide a scientific basis for the future studies that look for the drugs and behavioral interventions to prevent and treat the cognition and memory dysfunction in AD.

老年性痴呆（AD）是一种以进行性认知功能障碍和记忆损害为主的中枢神经系统退行性疾病，而空间认知和学习记忆等高级功能与海马结构密切相关。我们在国际上首次阐述了定量研究有髓神经纤维的体视学方法，并且运用这些方法在近期的研究中发现，出现空间记忆和学习能力下降的转基因AD小鼠海马齿状回内有髓神经纤维总长度显著性降低。而大脑比我们想象的具有更大的可塑性，一些研究发现跑步锻炼可能延缓AD的进程，但其作用的神经生物学基础尚不清楚。因此，我们拟对转基因AD小鼠学习记忆改变前和改变后分别给予跑步干预，运用行为学方法、体视学方法与电镜、免疫组织化学相结合的方法研究跑步锻炼对不同时期转基因AD小鼠学习记忆能力和海马结构的影响，以期进一步认识跑步锻炼对AD大脑认知和记忆功能的作用以及发挥这些作用的结构基础，从而为寻找预防和治疗AD认知和记忆功能下降的药物和行为学手段提供科学依据。

阿尔兹海默氏病（AD）是一种以进行性认知功能障碍和记忆损害为主的中枢神经系统退行性疾病，而空间认知和学习记忆等高级功能与海马结构密切相关。而大脑比我们想象的具有更大的可塑性，一些研究发现跑步锻炼可能延缓AD的进程，但其作用的神经生物学基础尚不清楚。因此，我们对转基因AD小鼠学习记忆改变前和改变后分别给予跑步锻炼干预，并运用行为学方法、体视学方法与电镜技术、免疫荧光相结合的方法研究跑步锻炼对不同时期转基因AD小鼠学习记忆能力、海马结构的影响，以期进一步认识跑步锻炼对AD大脑认知和记忆功能的作用以及发挥这些作用的结构基础。我们主要的研究发现是：跑步锻炼对转基因AD小鼠行为学改变前和改变后的空间学习记忆能力均具有积极的改善作用；跑步锻炼可以明显增加早期转基因AD小鼠大脑海马和各亚区的体积；跑步锻炼可以显著减少转基因AD小鼠海马及海马亚区内神经元的丢失；跑步锻炼可以明显延缓转基因AD小鼠海马内有髓神经纤维和髓鞘的丢失；跑步锻炼可以增加转基因AD小鼠大脑白质体积、白质内有髓神经纤维总体积和有髓神经纤维轴突体积；跑步锻炼可以改善转基因AD小鼠大脑白质内毛细血管的总体积、总表面和总长度的下降。这些研究结果为跑步锻炼改善转基因AD小鼠大脑功能提供了重要的形态学基础，也为将来寻找防治AD进程的手段提供了重要的“靶结构”，为寻找延缓AD进程的行为学手段提供了重要的依据。