Abstract
Memories are assumed to be formed by sets of synapses changing their structural or functional performance. The efficacy of forming new memories declines with advancing age, but the synaptic changes underlying age-induced memory impairment remain poorly understood. Recently, we found spermidine feeding to specifically suppress age-dependent impairments in forming olfactory memories, providing a mean to search for synaptic changes involved in age-dependent memory impairment. Here, we show that a specific synaptic compartment, the presynaptic active zone (AZ), increases the size of its ultrastructural elaboration and releases significantly more synaptic vesicles with advancing age. These age-induced AZ changes, however, were fully suppressed by spermidine feeding. A genetically enforced enlargement of AZ scaffolds (four gene-copies of BRP) impaired memory formation in young animals. Thus, in the Drosophila nervous system, aging AZs seem to steer towards the upper limit of their operational range, limiting synaptic plasticity and contributing to impairment of memory formation. Spermidine feeding suppresses age-dependent memory impairment by counteracting these age-dependent changes directly at the synapse.
Highlights
Age-dependent memory impairment (AMI), which is associated with both psychiatric and neurodegenerative disorders, starts in midlife and worsens with advancing age, suggesting that the greatest driving factor is age itself
Using the fly Drosophila melanogaster as a model, we found that feeding them spermidine —a polyamine compound—suppresses age-induced decline in olfactory memory, providing us with a tool to further decipher mechanisms associated with age-dependent memory impairment
We set out to determine the role of age-induced changes in the organization and function of synapses in AMI, using dietary supplementation with spermidine as a tool to identify synaptic changes that can potentially contribute to AMI
Summary
Age-dependent memory impairment (AMI), which is associated with both psychiatric and neurodegenerative disorders, starts in midlife and worsens with advancing age, suggesting that the greatest driving factor is age itself. Animal models that allow one to monitor physiological changes across their lifespan and to test for a causal character of age-induced changes might be helpful in exploring the mechanistic basis of AMI. D. melanogaster, with its short lifespan of around 60 d and advanced molecular genetic tools, provides an efficient experimental model to unravel mechanisms underlying AMI. Aversive short-, intermediate-, and long-term olfactory memories have been found to be subject to age-induced decline in Drosophila, with an onset at about 10 d of age and plateaus at about 30 d of age [2,3,4,5,6]. We recently found a simple dietary supplementation of spermidine, a polyamine that protects from AMI in Drosophila
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