BROWSE

Related Scientist

ccs's photo.

ccs
인지및사회성연구단
more info

ITEM VIEW & DOWNLOAD

Visualizing reactive astrocyte-neuron interaction in Alzheimer's disease using C-11-acetate and F-18-FDG

Cited 0 time in webofscience Cited 0 time in scopus
162 Viewed 0 Downloaded
Title
Visualizing reactive astrocyte-neuron interaction in Alzheimer's disease using C-11-acetate and F-18-FDG
Author(s)
Nam, Min-Ho; Ko, Hae Young; Kim, Dongwoo; Lee, Sangwon; Yongmin Mason Park; Seung Jae Hyeon; Woojin Won; Chung, Jee-In; Kim, Seon Yoo; Jo, Han Hee; Oh, Kyeong Taek; Han, Young-Eun; Lee, Gwan-Ho; Yeon Ha Ju; Lee, Hyowon; Kim, Hyunjin; Heo, Jaejun; Mridula Bhalla; Ki Jung Kim; Jea Kwon; Stein, Thor D.; Kong, Mingyu; Lee, Hyunbeom; Lee, Seung Eun; Oh, Soo-Jin; Chun, Joong-Hyun; Park, Mi-Ae; Park, Ki Duk; Ryu, Hoon; Yun, Mijin; C. Justin Lee
Publication Date
2023-07
Journal
BRAIN, v.146, no.7, pp.2957 - 2974
Publisher
OXFORD UNIV PRESS
Abstract
Reactive astrogliosis is a hallmark of Alzheimer's disease (AD). However, a clinically validated neuroimaging probe to visualize the reactive astrogliosis is yet to be discovered. Here, we show that PET imaging with C-11-acetate and F-18-fluorodeoxyglucose (F-18-FDG) functionally visualizes the reactive astrocyte-mediated neuronal hypometabolism in the brains with neuroinflammation and AD. To investigate the alterations of acetate and glucose metabolism in the diseased brains and their impact on the AD pathology, we adopted multifaceted approaches including microPET imaging, autoradiography, immunohistochemistry, metabolomics, and electrophysiology. Two AD rodent models, APP/PS1 and 5xFAD transgenic mice, one adenovirus-induced rat model of reactive astrogliosis, and post-mortem human brain tissues were used in this study. We further curated a proof-of-concept human study that included C-11-acetate and F-18-FDG PET imaging analyses along with neuropsychological assessments from 11 AD patients and 10 healthy control subjects. We demonstrate that reactive astrocytes excessively absorb acetate through elevated monocarboxylate transporter-1 (MCT1) in rodent models of both reactive astrogliosis and AD. The elevated acetate uptake is associated with reactive astrogliosis and boosts the aberrant astrocytic GABA synthesis when amyloid-beta is present. The excessive astrocytic GABA subsequently suppresses neuronal activity, which could lead to glucose uptake through decreased glucose transporter-3 in the diseased brains. We further demonstrate that C-11-acetate uptake was significantly increased in the entorhinal cortex, hippocampus and temporo-parietal neocortex of the AD patients compared to the healthy controls, while F-18-FDG uptake was significantly reduced in the same regions. Additionally, we discover a strong correlation between the patients' cognitive function and the PET signals of both C-11-acetate and F-18-FDG. We demonstrate the potential value of PET imaging with C-11-acetate and F-18-FDG by visualizing reactive astrogliosis and the associated neuronal glucose hypometablosim for AD patients. Our findings further suggest that the acetate-boosted reactive astrocyte-neuron interaction could contribute to the cognitive decline in AD.
URI
https://pr.ibs.re.kr/handle/8788114/13619
DOI
10.1093/brain/awad037
ISSN
0006-8950
Appears in Collections:
Center for Cognition and Sociality(인지 및 사회성 연구단) > 1. Journal Papers (저널논문)
Files in This Item:
There are no files associated with this item.

qrcode

  • facebook

    twitter

  • Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse