Aleogho Binta Maria, Mohri Mizuho, Jang Moon Sun, Tsukada Sachio, Al-Hebri Yana, Matsuyama Hironori J, Tsukada Yuki, Mori Ikue, Noma Kentaro
Group of Microbial Motility, Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan.
Group of Nutritional Neuroscience, Neuroscience Institute, Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan.
Proc Natl Acad Sci U S A. 2025 Jan 7;122(1):e2412391122. doi: 10.1073/pnas.2412391122. Epub 2024 Dec 31.
Age-dependent sensory impairment, memory loss, and cognitive decline are generally attributed to neuron loss, synaptic dysfunction, and decreased neuronal activities over time. Concurrently, increased neuronal activity is reported in humans and other organisms during aging. However, it is unclear whether neuronal hyperactivity is the cause of cognitive impairment or a compensatory mechanism of circuit dysfunction. The roundworm exhibits age-dependent declines in an associative learning behavior called thermotaxis, in which its temperature preference on a thermal gradient is contingent on food availability during its cultivation. Cell ablation and calcium imaging demonstrate that the major thermosensory circuit consisting of AFD thermosensory neuron and AIY interneuron is relatively intact in aged animals. On the other hand, ablation of either AWC sensory neurons or AIA interneurons ameliorates the age-dependent thermotaxis decline. Both neurons showed spontaneous and stochastic hyperactivity in aged animals, enhanced by reciprocal communication between AWC and AIA via neurotransmitters and neuropeptides. Our findings suggest that AWC and AIA hyperactivity mediates thermotaxis decline in aged animals. Furthermore, dietary modulation could ameliorate age-dependent thermotaxis decline by suppressing neuronal hyperactivity. We propose that aberrantly enhanced, not diminished, neuronal activities can impair the behavior of aged animals.
年龄依赖性的感觉障碍、记忆力丧失和认知衰退通常归因于神经元丢失、突触功能障碍以及随着时间推移神经元活动的减少。与此同时，有报道称在衰老过程中人类和其他生物体内的神经元活动会增加。然而，目前尚不清楚神经元活动亢进是认知障碍的原因还是电路功能障碍的一种代偿机制。蛔虫在一种称为趋温性的联想学习行为中表现出年龄依赖性的衰退，即在其培养过程中，它在热梯度上的温度偏好取决于食物的可获得性。细胞消融和钙成像表明，由AFD热感觉神经元和AIY中间神经元组成的主要热感觉回路在老年动物中相对完整。另一方面，AWC感觉神经元或AIA中间神经元的消融可改善年龄依赖性的趋温性衰退。在老年动物中，这两种神经元均表现出自发性和随机性的活动亢进，通过神经递质和神经肽在AWC和AIA之间的相互通讯而增强。我们的研究结果表明，AWC和AIA的活动亢进介导了老年动物趋温性的衰退。此外，饮食调节可通过抑制神经元活动亢进来改善年龄依赖性的趋温性衰退。我们提出，异常增强而非减弱的神经元活动会损害老年动物的行为。
