Dustin Loren V. Almanza, Andrea Trevisiol, Margaret M. Koletar, Aaron Y. Lai, Jessica A. Ribeiro, Mary E. Hill, Greg J. Stanisz, JoAnne McLaurin, Bojana Stefanovic
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引用次数: 0
Abstract
INTRODUCTION
Alzheimer's disease (AD) involves progressive hippocampal dysfunction and atrophy. Obesity, common in AD patients, is a known dementia risk factor. Studying their interaction is difficult in humans due to AD's slow progression. Experimental AD models comorbid with obesity are needed for translational insights. This study examined the effects of a high-carbohydrate, high-fat (HCHF) diet in 12-month-old TgF344-AD rats.
METHODS
Nontransgenic (nTg) and TgAD rats received CHOW or CHOW and HCHF diet items from 9 to 12 months of age. Hippocampal neurovascular function was assessed using pseudo continuous arterial spin labeling (pCASL)-MRI during forepaw stimulation. Neuronal activity was recorded with Neuropixels probes.
RESULTS
CHOW-fed TgAD rats showed reduced hippocampal cerebral blood flow (CBF), CBF changes spread, and neuronal power responses to somatosensory stimulation; all of these deficits were improved on the HCHF diet.
DISCUSSION
This approach provides a sensitive, task-free assay of hippocampal neurovascular coupling. The transiently improved neurovascular and electrophysiological metrics in HCHF-fed TgAD rats may be a manifestation of metabolically dysregulated AD brain benefitting from increased metabolite availability.
Highlights
Pseudo-continuous arterial spin labeling (pCASL) magnetic resonance imaging (MRI) -based characterization of hippocampal functional hyperemia.
Hippocampal functional hyperemia is attenuated in symptomatic Alzheimer's disease (AD) pathology.
A high-carbohydrate, high-fat (HCHF) diet transiently restores hippocampal functional hyperemia in symptomatic AD pathology.
期刊介绍:
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.