关键词: Alzheimer’s disease Insulin Metabolism Spatial learning and memory Treadmill exercise

Mesh : Animals Alzheimer Disease / metabolism drug therapy therapy Insulin-Like Growth Factor I / metabolism Physical Conditioning, Animal Male Insulin / metabolism Disease Models, Animal Rats Hypothalamus / metabolism Rats, Wistar Signal Transduction / drug effects Glucose Transporter Type 4 / metabolism genetics Amyloid beta-Peptides / metabolism Brain-Derived Neurotrophic Factor / metabolism genetics Hippocampus / metabolism drug effects Administration, Intranasal Peptide Fragments Spatial Memory / drug effects Spatial Learning / drug effects

来  源:   DOI:10.1038/s41598-024-66637-2   PDF(Pubmed)

Abstract:
Alzheimer\'s disease (AD) is a neurological condition that is connected with a decline in a person\'s memory as well as their cognitive ability. One of the key topics of AD research has been the exploration of metabolic causes. We investigated the effects of treadmill exercise and intranasal insulin on learning and memory impairment and the expression of IGF1, BDNF, and GLUT4 in hypothalamus. The animals were put into 9 groups at random. In this study, we examined the impact of insulin on spatial memory in male Wistar rats and analyzed the effects of a 4-week pretreatment of moderate treadmill exercise and insulin on the mechanisms of improved hypothalamic glucose metabolism through changes in gene and protein expression of IGF1, BDNF, and GLUT4. We discovered that rat given Aβ25-35 had impaired spatial learning and memory, which was accompanied by higher levels of Aβ plaque burden in the hippocampus and lower levels of IGF1, BDNF, and GLUT4 mRNA and protein expression in the hypothalamus. Additionally, the administration of exercise training and intranasal insulin results in the enhancement of spatial learning and memory impairments, the reduction of plaque burden in the hippocampus, and the enhancement of the expression of IGF1, BDNF, and GLUT4 in the hypothalamus of rats that were treated with Aβ25-35. Our results show that the improvement of learning and spatial memory due to the improvement of metabolism and upregulation of the IGF1, BDNF, and GLUT4 pathways can be affected by pretreatment exercise and intranasal insulin.
摘要:
阿尔茨海默病(AD)是一种神经系统疾病,与人的记忆力和认知能力下降有关。AD研究的关键主题之一是探索代谢原因。我们研究了跑步机运动和鼻内胰岛素对学习和记忆障碍的影响以及IGF1,BDNF的表达,和GLUT4在下丘脑。将动物随机分为9组。在这项研究中,我们研究了胰岛素对雄性Wistar大鼠空间记忆的影响,并分析了4周的适度跑步机运动和胰岛素预处理对通过改变IGF1,BDNF的基因和蛋白质表达改善下丘脑葡萄糖代谢的机制的影响,GLUT4我们发现给予Aβ25-35的大鼠空间学习和记忆受损,伴随着海马中较高水平的Aβ斑块负荷和较低水平的IGF1,BDNF,和GLUT4mRNA和蛋白在下丘脑中的表达。此外,运动训练和鼻内胰岛素的管理导致空间学习和记忆障碍的增强,减少海马中的斑块负担,IGF1、BDNF的表达增强,和用Aβ25-35治疗的大鼠下丘脑中的GLUT4。我们的结果表明,由于IGF1,BDNF的代谢和上调的改善,学习和空间记忆的改善,和GLUT4途径可以通过预处理运动和鼻内胰岛素的影响。
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