高热量摄入可挽救早期症状性ad诱导的海马神经血管偶联缺陷。

IF 11.1 1区 医学 Q1 CLINICAL NEUROLOGY
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

摘要

阿尔茨海默病(AD)涉及进行性海马功能障碍和萎缩。肥胖在阿尔茨海默病患者中很常见,是已知的痴呆风险因素。由于阿尔茨海默病的进展缓慢,研究它们之间的相互作用在人类身上很困难。实验AD模型与肥胖共病需要翻译的见解。本研究检测了高碳水化合物、高脂肪(HCHF)饮食对12个月大的TgF344-AD大鼠的影响。方法非转基因(nTg)和TgAD大鼠于9 ~ 12月龄分别饲喂CHOW或CHOW + HCHF饲料。在前爪刺激时,使用伪连续动脉自旋标记(pCASL)-MRI评估海马神经血管功能。用Neuropixels探针记录神经元活动。结果低负荷喂养的TgAD大鼠海马脑血流量(CBF)减少,CBF变化扩散性减弱,体感觉刺激下神经元能量反应减弱;所有这些缺陷都在HCHF饮食中得到改善。这种方法提供了一种敏感的,无任务的海马体神经血管耦合分析。在hchf喂养的TgAD大鼠中,神经血管和电生理指标的短暂改善可能是代谢失调的AD脑受益于代谢物可用性增加的表现。基于磁共振成像(MRI)的海马功能性充血的超连续动脉自旋标记(pCASL)表征海马体功能性充血在症状性阿尔茨海默病(AD)病理中减弱。高碳水化合物,高脂肪(HCHF)饮食暂时恢复海马体功能性充血症状AD病理。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
High-caloric intake rescues early symptomatic AD-induced hippocampal neurovascular coupling deficits

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.
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来源期刊
Alzheimer's & Dementia
Alzheimer's & Dementia 医学-临床神经学
CiteScore
14.50
自引率
5.00%
发文量
299
审稿时长
3 months
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.
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