Effect Of Aging And Related Stresses On Learning And Memory In C. Elegans

In the process of normal aging and neurodegeneration,memory loss or cognitive deficit is one of the most representative symptoms while response to stresses such as protein aggregation and oxidative stress is one of the most important molecular mechanisms.Therefore,it is important to understand the regulation of learning and memory in response to aging-related stresses.Here we use Caenorhabditis elegans as a model to study the potential effects of these stresses on learning and memory.First,we found that the learning and memory capabilities of wild-type worms（N2）were gradually decreased with aging.Then,we compared the learning and memory of protein aggregation C.elegans models AM141 and AM140 and found that their learning and memory capacities were significantly higher than that of N2 worms in early-and mid-aging stages.However,such protein aggregation was found to have negative impacts on the motility and body size of adult worms.Interesting,the learning and memory of HA759 C.elegans,a neurotoxic model of protein aggregation,were almost the same with that of N2 worms.Recent studies reported that early oxidative stress may prolong the lifespan of C.elegans,and therefore we further investigated the effect of oxidative stress on learning and memory in C.elegans.We found that,when not affecting the survival of worms,oxidative stress induced by TBHP,H₂O₂or high-sugar diet was able to improve the learning and memory ability of C.elegans.We also found that the oxidative stress experienced in dauer stages or in adulthood showed similar effect on the learning and memory of adult worms,while the oxidative stress experienced in dauer stages had negative impacts on the motility and body size of adult worms.Further analysis revealed that the reactive oxygen species in the above TBHP-treated worms was increased,indicating the existence of oxidative stress.The activities of antioxidant enzymes such as superoxide dismutase and catalase as well as the expression levels of antioxidant enzymes-related genes sod-3,ctl-2 were found not affected.However,the expression level of cytochrome P450related gene cyp-13A1 was decreased significantly,further implying the activation of oxidative stress response and relevant metabolism.Taken together,these results demonstrate that aging-related stress such as protein aggregation and oxidative stress could improve the learning and memory ability of C.elegans to a certain extent,providing a basis for further investigation on aging-related phenotypes and diseases and an insight into their applications in screening of active ingredients in foods and drugs.