Murakami Shin
Gheens Center on Aging, Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY, USA.
Mol Neurobiol. 2007 Feb;35(1):85-94. doi: 10.1007/BF02700625.
The nematode Caenorhabditis elegans is an excellent model organism to study biological processes relevant to a wide variety of human and rodent disease systems. Previous studies have suggested that mutants of the insulin/insulin-like growth factor-1 pathway show life extension and increased stress resistance in various species, including C. elegans, the fruit fly, and the mouse. It has recently been shown that the life-extending mutants, including the age-1 phosphatidylinositol- 3 OH kinase mutants and the daf-2 insulin-like receptor mutants, display improvement in a type of associative learning behavior called thermotaxis learning behavior. The age-1 mutant shows a dramatic threefold extension of the health-span that ensures thermotaxis learning behavior, suggesting strong neuroprotective actions during aging. The age-1 and daf-2 mutants show resistance to multiple forms of stress and upregulates the genes involved in reactive oxygen species scavenging, heat shock, and P450 drug-detoxification. The life-extending mutants may confer resistance to various stress and diseases in neurons. Therefore, C. elegans provides an emerging system for the prevention of age-related deficits in the nervous system and in learning behaviors. This article discusses the aging of learning and memory and the neuroprotection effects of life-extending mutants on learning behaviors.
线虫秀丽隐杆线虫是研究与多种人类和啮齿动物疾病系统相关生物过程的优秀模式生物。先前的研究表明,胰岛素/胰岛素样生长因子-1信号通路的突变体在包括秀丽隐杆线虫、果蝇和小鼠在内的各种物种中表现出寿命延长和应激抗性增强。最近有研究表明,包括age-1磷脂酰肌醇-3羟基激酶突变体和daf-2胰岛素样受体突变体在内的寿命延长突变体,在一种称为趋温性学习行为的联想学习行为中表现出改善。age-1突变体的健康寿命显著延长了三倍,确保了趋温性学习行为,这表明在衰老过程中具有强大的神经保护作用。age-1和daf-2突变体对多种形式的应激具有抗性,并上调了参与活性氧清除、热休克和P450药物解毒的基因。寿命延长突变体可能赋予神经元对各种应激和疾病的抗性。因此,秀丽隐杆线虫为预防神经系统和学习行为中与年龄相关的缺陷提供了一个新兴的系统。本文讨论了学习和记忆的衰老以及寿命延长突变体对学习行为的神经保护作用。