Detection of sex-specific glutamate changes in subregions of hippocampus in an early-stage Alzheimer's disease mouse model using GluCEST MRI

IF 11.1 1区医学 Q1 CLINICAL NEUROLOGY Alzheimer's & Dementia Pub Date : 2024-09-11 DOI:10.1002/alz.14190

Narayan Datt Soni, Anshuman Swain, Halvor Juul, Quy Cao, Mohammad Haris, David A. Wolk, Virginia M.-Y. Lee, John A. Detre, Ravi Prakash Reddy Nanga, Ravinder Reddy

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Abstract

INTRODUCTION

Regional glucose hypometabolism resulting in glutamate loss has been shown as one of the characteristics of Alzheimer's disease (AD). Because the impact of AD varies between the sexes, we utilized glutamate-weighted chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI) for high-resolution spatial mapping of cerebral glutamate and investigated subregional changes in a sex-specific manner.

METHODS

Eight-month-old male and female AD mice harboring mutant amyloid precursor protein (APP^NL-F/NL-F: n = 36) and wild-type (WT: n = 39) mice underwent GluCEST MRI, followed by proton magnetic resonance spectroscopy (¹H-MRS) in hippocampus and thalamus/hypothalamus using 9.4T preclinical MR scanner.

RESULTS

GluCEST measurements revealed significant (p ≤ 0.02) glutamate loss in the entorhinal cortex (% change ± standard error: 8.73 ± 2.12%), hippocampus (11.29 ± 2.41%), and hippocampal fimbriae (19.15 ± 2.95%) of male AD mice. A similar loss of hippocampal glutamate in male AD mice (11.22 ± 2.33%; p = 0.01) was also observed in ¹H-MRS.

DISCUSSIONS

GluCEST MRI detected glutamate reductions in the fimbria and entorhinal cortex of male AD mice, which was not reported previously. Resilience in female AD mice against these changes indicates an intact status of cerebral energy metabolism.

Highlights

Glutamate levels were monitored in different brain regions of early-stage Alzheimer's disease (AD) and wild-type male and female mice using glutamate-weighted chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI).

Male AD mice exhibited significant glutamate loss in the hippocampus, entorhinal cortex, and the fimbriae of the hippocampus.

Interestingly, female AD mice did not have any glutamate loss in any brain region and should be investigated further to find the probable cause.

These findings demonstrate previously unreported sex-specific glutamate changes in hippocampal sub-regions using high-resolution GluCEST MRI.

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利用 GluCEST MRI 检测阿尔茨海默病早期小鼠模型海马亚区谷氨酸的性别特异性变化

阿尔茨海默病（AD）的特征之一是区域葡萄糖代谢不足，导致谷氨酸丢失。由于阿兹海默症对两性的影响不同，我们利用谷氨酸加权化学交换饱和转移（GluCEST）磁共振成像（MRI）来绘制脑谷氨酸的高分辨率空间图，并以性别特异性的方式研究亚区域的变化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

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.