The complex relationship between late-onset caloric restriction and synaptic plasticity in aged Wistar rats

Abstract

Age-related reduction in spine density, synaptic marker expression, and synaptic efficiency are frequently reported. These changes provide the cellular andmolecular basis for the cognitive decline characteristic for old age. Nevertheless, there are several approaches that have the potential to ameliorate theseprocesses and improve cognition, caloric restriction being one of the mostpromising and widely studied. While lifelong caloric restriction is known forits numerous beneficial effects, including improved cognitive abilities andincreased expression of proteins essential for synaptic structure and function,the effects of late-onset and/or short-term CR on synaptic plasticity have yet tobe investigated. We have previously documented that the effects of CR arestrongly dependent on whether CR is initiated in young or old subjects. Withthis in mind, we conducted a long-term study in aging Wistar rats to examinechanges in the expression of several key synaptic markers under the regimenof CR started at different time points in life. We found a significant increase inthe expression of both presynaptic and postsynaptic markers. However, takinginto account previously reported changes in the behavior detected in these animals, we consider that this increase cannot represent beneficial effect of CR.