Alterations to Cerebral Perfusion, Metabolite Profiles, and Neuronal Morphology in the Hippocampus and Cortex of Male and Female Mice during Chronic Exposure to a High-Salt Diet

Abstract

Excess dietary salt reduces resting cerebral blood flow (CBF) and vascular reactivity, which can limit the fueling of neuronal metabolism. It is hitherto unknown whether metabolic derangements induced by high-salt-diet (HSD) exposure during adulthood are reversed by reducing salt intake. In this study, male and female mice were fed an HSD from 9 to 16 months of age, followed by a normal-salt diet (ND) thereafter until 23 months of age. Controls were continuously fed either ND or HSD. CBF and metabolite profiles were determined longitudinally by arterial spin labeling magnetic resonance imaging and magnetic resonance spectroscopy, respectively. HSD reduced cortical and hippocampal CBF, which recovered after dietary salt normalization, and affected hippocampal but not cortical metabolite profiles. Compared to ND, HSD increased hippocampal glutamine and phosphocreatine levels and decreased creatine and choline levels. Dietary reversal only allowed recovery of glutamine levels. Histology analyses revealed that HSD reduced the dendritic arborization and spine density of cortical and hippocampal neurons, which were not recovered after dietary salt normalization. We conclude that sustained HSD exposure throughout adulthood causes permanent structural and metabolic alterations to the mouse brain that are not fully normalized by lowering dietary salt during aging.

CT- and MRI-Aided Fluorescence Tomography Reconstructions for Biodistribution Analysis

“…Besides using MRI for FLT reconstruction, adding MRI allows to additionally perform a range of functional analyses for characterizing tissue properties to assess therapeutic or toxic effects. [14][15][16][17]55 In summary, the comprehensiveness and robustness of biodistribution studies can be improved by a CT-MRI-FLT hybrid imaging approach. The required hybridization was realized via markers placed in the mouse holder, which is a pragmatic, adaptable, and generalizable approach for combining multiple imaging modalities.…”

“…Furthermore, it enables multiple functional and metabolic analyses, for example, by applying arterial spin labeling, functional MRI, blood oxygenation level-dependent imaging, chemical exchange saturation transfer, and diffusion-weighted sequences, as well as MR spectroscopy. [14][15][16][17] Academic sites already merged FLT with MRI and developed simultaneous and sequential MRI-FLT applications. [18][19][20] Simultaneous MRI-FLT reduces scanning time and has been used for tumor imaging but requires complex engineering to make the FLT compatible with the high magnetic field strengths.…”

Genetic deletion of hormone‐sensitive lipase in mice reduces cerebral blood flow but does not aggravate the impact of diet‐induced obesity on memory

“…HSL−/−, HSL+/−, and HSL+/+ mice of either sex were housed in groups of 2–5 animals on a 12‐hour light–dark cycle with lights on at 7:00, room temperature of 21–23°C, and humidity of 55%–60%. Power calculations were not performed, but minimum sample size was estimated from previous CBF measurements in mice (Meissner et al., 2022). For each litter, mice were assigned a random number using the RAND function in Excel (Microsoft, Redmond, WA, USA) and, following ascending sort, mice with lowest and highest numbers were respectively assigned to be fed control diet (CD) or high‐fat diet (HFD).…”

“…Arterial spin labeling (ASL) magnetic resonance imaging (MRI) was performed after 8 weeks of diet intervention, as previously reported (Meissner et al., 2022). Briefly, mice were scanned on a 9.4T Bruker BioSpec AV III (Bruker, Ettlingen, Germany) with bore size of 86 mm and gradient strength of 670 mT/m, using a quadrature volume resonator coil for transmission and a 20‐mm linear surface loop coil for reception.…”

“…HSL−/−, HSL+/−, and HSL+/+ mice of either sex were housed in groups of 2-5 animals on a 12-hour light-dark cycle with lights on at 7:00, room temperature of 21-23°C, and humidity of 55%-60%. Power calculations were not performed, but minimum sample size was estimated from previous CBF measurements in mice (Meissner et al, 2022).…”