Caloric restriction and aging but not overexpression of SOD1 affect hippocampal volumes in mice

Caloric restriction (CR) and antioxidants have been proposed as strategies to attenuate age-related brain changes. The hippocampus and its subregions dentate gyrus (DG). CA3 and CA1-2 show vulnerability to aging, with hippocampal volume alterations as a measurable sign. Using design-based stereological techniques, we investigated the volumes of the hippocampus and its subregions in six 12-month-old and six 24-month-old mice that were randomly selected from four aging cohorts of 60 male mice each: (1) wild-type mice (WT) fed with control diet (CD), (2) transgenic mice oxerexpressing normal human SOD1 fed with CD, (3) WT mice fed with CR diet, and (4) SOD1 mice fed with CR diet. Aging reduced the mean volume of the entire hippocampus (-9.5%), grey (-8.7%) and white matter (-9.7%), and CA3 subregion (-13.6%), but not DG or CA1-2 subregion. CR reduced the mean volumes of every hippocampal region investigated (on average 11%) in both 12-month-old, and 24-month-old mice. Overexpression of SOD1 was not associated with any volume alteration. These findings indicate that although aging and CR in mice are both associated with hippocampal volume reductions, the patterns of the volume reductions differ. These morphometric alterations may have impact on the function of the hippocampus during aging and CR.