Mackenzie M Spicer, Jianqi Yang, Daniel Fu, Alison N DeVore, Marisol Lauffer, Nilufer S Atasoy, Deniz Atasoy, Rory A Fisher
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引用次数: 0
摘要
海马神经元缺失会导致阿尔茨海默病（AD）患者出现认知功能障碍。阿尔茨海默病患者的成年海马神经元生成（AHN）会减少。运动能刺激啮齿类动物的海马神经发生，改善记忆力并减缓阿尔茨海默病患者的认知能力衰退。然而，人们对运动诱导 AHN 和改善 AD 认知的分子途径知之甚少。在这里，我们发现 APP SWE 小鼠的自主跑步可使其海马认知障碍恢复到对照组小鼠的水平。在齿状回（DG）神经元祖细胞（NPs）中缺失 RGS6 后，这种认知功能的恢复被取消，同时也取消了跑步介导的 AHN 增加。与对照组小鼠相比，久坐的 APP SWE 小鼠的 AHN 有所降低，DG NPs 中的 RGS6 缺失会降低基础 AHN。RGS6在AD患者DG中的表达明显降低。因此，RGS6介导了运动诱导的对AD小鼠认知受损和AHN的拯救，从而确定了DG NPs中的RGS6是对抗AD海马神经元丢失的潜在靶点：在APP SWE小鼠中，海马NPCs中RGS6的表达促进了自主跑步诱导的神经发生并恢复了认知能力：RGS6、阿尔茨海默病、成人海马神经发生、神经前体细胞、齿状回、运动、学习/记忆。
RGS6 mediates exercise-induced recovery of hippocampal neurogenesis, learning, and memory in an Alzheimer's mouse model.
Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer's disease (AD). Adult hippocampal neurogenesis (AHN) is reduced in AD patients. Exercise stimulates AHN in rodents and improves memory and slows cognitive decline in AD patients. However, the molecular pathways for exercise-induced AHN and improved cognition in AD are poorly understood. Here, we show that voluntary running in APP SWE mice restores their hippocampal cognitive impairments to that of control mice. This cognitive rescue was abolished by RGS6 deletion in dentate gyrus (DG) neuronal progenitors (NPs), which also abolished running-mediated increases in AHN. AHN was reduced in sedentary APP SWE mice versus control mice, with basal AHN reduced by RGS6 deletion in DG NPs. RGS6 expression is significantly lower in the DG of AD patients. Thus, RGS6 mediates exercise-induced rescue of impaired cognition and AHN in AD mice, identifying RGS6 in DG NPs as a potential target to combat hippocampal neuron loss in AD.
Teaser: RGS6 expression in hippocampal NPCs promotes voluntary running-induced neurogenesis and restored cognition in APP SWE mice.
期刊介绍：
Nutrition & Food Science* (NFS) is an international, double blind peer-reviewed journal offering accessible and comprehensive coverage of food, beverage and nutrition research. The journal draws out the practical and social applications of research, demonstrates best practice through applied research and case studies and showcases innovative or controversial practices and points of view. The journal is an invaluable resource to inform individuals, organisations and the public on modern thinking, research and attitudes to food science and nutrition. NFS welcomes empirical and applied research, viewpoint papers, conceptual and technical papers, case studies, meta-analysis studies, literature reviews and general reviews which take a scientific approach to the following topics: -Attitudes to food and nutrition -Healthy eating/ nutritional public health initiatives, policies and legislation -Clinical and community nutrition and health (including public health and multiple or complex co-morbidities) -Nutrition in different cultural and ethnic groups -Nutrition during pregnancy, lactation, childhood, and young adult years -Nutrition for adults and older people -Nutrition in the workplace -Nutrition in lower and middle income countries (incl. comparisons with higher income countries) -Food science and technology, including food processing and microbiological quality -Genetically engineered foods -Food safety / quality, including chemical, physical and microbiological analysis of how these aspects effect health or nutritional quality of foodstuffs
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