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

Moderate loss of cerebellar Purkinje cells after chronic bilateral common carotid artery occlusion in rats

Pathological effects of moderate ischemia (oligemia, hypoperfusion) are relevant in relation to vascular factors in dementia. Chronic bilateral common carotid artery occlusion (BCCAO) in adult Wistar rats induces oligemia and leads to acute changes in gene expression, subacute changes in cortical astrocytes and prolonged changes in white matter tracts, while largely sparing neurons in the forebrain areas. Dilation and remodeling of the basilar artery ensures blood flow to the forebrain. The present study examined the hypoxia-sensitive Purkinje cells in the cerebellum after 6 months of BCCAO using conventional neuropathological analysis, immunohistochemistry and high-precision design-based stereologic methods. Purkinje cells in the vermis region revealed abnormally shaped nuclei. A stereologic analysis showed that the mean total number of Purkinje cells within the vermis was statistically significantly smaller in the BCCAO animals than in the control animals (d = 11.8%; P < 0.0001). BCCAO had no significant effect on the mean volumes of the molecular layer, granule cell layer and white matter in the vermis or the entire cerebellum. Remodeling of the basilar artery indicated that secondary vascular perturbations might be responsible for the effects of BCCAO on the cerebellar Purkinje cells

Hippocampal interneuron loss in an APP/PS1 double mutant mouse and in Alzheimer's disease.

Item does not contain fulltextHippocampal atrophy and neuron loss are commonly found in Alzheimer's disease (AD). However, the underlying molecular mechanisms and the fate in the AD hippocampus of subpopulations of interneurons that express the calcium-binding proteins parvalbumin (PV) and calretinin (CR) has not yet been properly assessed. Using quantitative stereologic methods, we analyzed the regional pattern of age-related loss of PV- and CR-immunoreactive (ir) neurons in the hippocampus of mice that carry M233T/L235P knocked-in mutations in presenilin-1 (PS1) and overexpress a mutated human beta-amyloid precursor protein (APP), namely, the APP(SL)/PS1 KI mice, as well as in APP(SL) mice and PS1 KI mice. We found a loss of PV-ir neurons (40-50%) in the CA1-2, and a loss of CR-ir neurons (37-52%) in the dentate gyrus and hilus of APP(SL)/PS1 KI mice. Interestingly, comparable PV- and CR-ir neuron losses were observed in the dentate gyrus of postmortem brain specimens obtained from patients with AD. The loss of these interneurons in AD may have substantial functional repercussions on local inhibitory processes in the hippocampus.01 maart 201