Caloric restriction in young rats disturbs hippocampal neurogenesis and spatial learning

It is widely known that caloric restriction (CR) has benefits on several organic systems, including the central nervous system. However, the majority of the CR studies was performed in adult animals and the information about the consequences on young populations is limited. In this study, we analyzed the effects of young-onset CR, started at 4 weeks of age, in the number of neuropeptide Y (NPY)-containing neurons and in neurogenesis of the hippocampal formation, using doublecortin (DCX) and Ki67 as markers. Knowing that CR treatment could interfere with exploratory activity, anxiety, learning and memory we have analyzed the performance of the rats in the open-field, elevated plus-maze and Morris water maze tests. Animals aged 4 weeks were randomly assigned to control or CR groups. Controls were maintained in the ad libitum regimen during 2 months. The adolescent CR rats were fed, during 2 months, with 60% of the amount of food consumed by controls. We have found that young-onset CR treatment did not affect the total number of NPY-immunopositive neurons in dentate hilus, CA3 and CA1 hippocampal subfields and did not change the exploratory activity and anxiety levels. Interestingly, we have found that young-onset CR might affect spatial learning process since those animals showed worse performance during the acquisition phase of Morris water maze. Furthermore, young-onset CR induced alterations of neurogenesis in the dentate subgranular layer that seems to underlie the impairment of spatial learning. Our data suggest that adolescent animals are vulnerable to CR treatment and that this diet is not suitable to be applied in this age phase.