Abstract
Age-related memory impairment (AMI) is a common feature and a debilitating phenotype of brain aging in many animals. However, the molecular mechanisms underlying AMI are still largely unknown. The cricket Gryllus bimaculatus is a useful experimental animal for studying age-related changes in learning and memory capability; because the cricket has relatively short life-cycle and a high capability of olfactory learning and memory. Moreover, the molecular mechanisms underlying memory formation in crickets have been examined in detail. In the present study, we trained male crickets of different ages by multiple-trial olfactory conditioning to determine whether AMI occurs in crickets. Crickets 3 weeks after the final molt (3-week-old crickets) exhibited levels of retention similar to those of 1-week-old crickets at 30 min or 2 h after training; however they showed significantly decreased levels of 1-day retention, indicating AMI in long-term memory (LTM) but not in anesthesia-resistant memory (ARM) in olfactory learning of crickets. Furthermore, 3-week-old crickets injected with a nitric oxide (NO) donor, a cyclic GMP (cGMP) analog or a cyclic AMP (cAMP) analog into the hemolymph before conditioning exhibited a normal level of LTM, the same level as that in 1-week-old crickets. The rescue effect by NO donor or cGMP analog injection was absent when the crickets were injected after the conditioning. For the first time, an NO donor and a cGMP analog were found to antagonize the age-related impairment of LTM formation, suggesting that deterioration of NO synthase (NOS) or molecules upstream of NOS activation is involved in brain-aging processes.
Highlights
Impairment of memorization ability in relation to aging (Age-related memory impairment, AMI) is a common feature of brain aging in many animal species, including humans (Yankner et al, 2008), insects (Tamura et al, 2003; Mery, 2007) and nematodes (Murakami and Murakami, 2005)
We showed that AMI occurs in crickets
Aged crickets failed to form long-term memory (LTM) even when they received 4 sets of differential conditioning, which is twice the number of trials sufficient for young adults to form LTM (Matsumoto and Mizunami, 2002a; Matsumoto et al, 2003). This defect in aged crickets was observed in LTM formation but not in anesthesia-resistant memory (ARM) formation
Summary
Impairment of memorization ability in relation to aging (Age-related memory impairment, AMI) is a common feature of brain aging in many animal species, including humans (Yankner et al, 2008), insects (Tamura et al, 2003; Mery, 2007) and nematodes (Murakami and Murakami, 2005). Recovery from AMI is one of the major challenges in human lives in order to maintain quality of life. To address this issue, it is important to clarify the neuronal and molecular mechanisms underlying AMI in the brain. A few studies on the fruit-fly Drosophila have shed light on the molecular mechanisms of AMI (Tamura et al, 2003; Yamazaki et al, 2007, 2010)
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