Promotion of astrocyte-neuron glutamate-glutamine shuttle by SCFA contributes to the alleviation of Alzheimer?s disease

被引:63
作者
Sun, Yan [1 ,2 ]
Zhang, Huaiwu [1 ,2 ]
Zhang, Xuan [2 ]
Wang, Wenzhao [3 ]
Chen, Yong [6 ]
Cai, Zhiyou [4 ]
Wang, Qihui [1 ,2 ]
Wang, Jun [2 ]
Shi, Yi [1 ,2 ,4 ,5 ,6 ]
机构
[1] Univ Chinese Acad Sci, Savaid Med Sch, Beijing, Peoples R China
[2] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China
[3] Chinese Acad Sci, Inst Microbiol, State Key Lab Mycol, Beijing, Peoples R China
[4] Univ Chinese Acad Sci, Chongqing Gen Hosp, Chongqing Key Lab Neurodegenerat Dis, Chongqing, Peoples R China
[5] Chinese Acad Sci, Ctr Influenza Rsearch & Early Warning CASCIRE, CAS TWAS Ctr Excellence Emerging Infect Dis CEEID, Beijing, Peoples R China
[6] Beijing Life Sci Acad BLSA, Beijing, Peoples R China
来源
REDOX BIOLOGY | 2023年 / 62卷
关键词
Alzheimer?s disease; Short chain fatty acids; Astrocyte; ROS; Neuroenergetics; Glutamate-glutamine shuttle; BRAIN ENERGY-METABOLISM; OXIDATIVE STRESS; SODIUM-BUTYRATE; FATTY-ACIDS; DNA-DAMAGE; SYSTEM; MODEL; MODULATION; LACTATE;
D O I
10.1016/j.redox.2023.102690
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The brain is particularly susceptible to oxidative damage which is a key feature of several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease. The shuttling of glutathione (GSH) precursors from astrocytes to neurons has been shown to be instrumental for the neuro-protective activity. Here, we revealed that short chain fatty acids (SCFA), which have been related to AD and PD, could promote glutamate-glutamine shuttle to potentially resist oxidative damage in neurons at cellular level. Furthermore, we performed nine-month-long dietary SCFA supplementations in APPswe/PS1dE9 (APP/PS1) mice, and showed that it reshaped the homeostasis of microbiota and alleviated the cognitive impairment by reducing A beta deposition and tau hyperphosphorylation. Single-cell RNA sequencing analysis of the hippocampus revealed SCFA can enhance astrocyte-neuron communication including glutamate-glutamine shuttle, mainly by acting on astrocyte in vivo. Collectively, our findings indicate that long-term dietary SCFA supplementations at early aging stage can regulate the neuroenergetics to alleviate AD, providing a promising direction for the development of new AD drug.
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页数:11
相关论文
共 59 条
  • [11] Glutamine uptake by neurons: Interaction of protons with system a transporters
    Chaudhry, FA
    Schmitz, D
    Reimer, RJ
    Larsson, P
    Gray, AT
    Nicoll, R
    Kavanaugh, M
    Edwards, RH
    [J]. JOURNAL OF NEUROSCIENCE, 2002, 22 (01) : 62 - 72
  • [12] Alzheimer's disease: strategies for disease modification
    Citron, Martin
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2010, 9 (05) : 387 - 398
  • [13] Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition
    Colombo, Alessio Vittorio
    Sadler, Rebecca Katie
    Llovera, Gemma
    Singh, Vikramjeet
    Roth, Stefan
    Heindl, Steffanie
    Monasor, Laura Sebastian
    Verhoeven, Aswin
    Peters, Finn
    Parhizkar, Samira
    Kamp, Frits
    de Aguero, Mercedes Gomez
    MacPherson, Andrew J.
    Winkler, Edith
    Herms, Jochen
    Benakis, Corinne
    Dichgans, Martin
    Steiner, Harald
    Giera, Martin
    Haass, Christian
    Tahirovic, Sabina
    Liesz, Arthur
    [J]. ELIFE, 2021, 10
  • [14] A cross-sectional comparison of brain glucose and ketone metabolism in cognitively healthy older adults, mild cognitive impairment and early Alzheimer's disease
    Croteau, E.
    Castellano, C. A.
    Fortier, M.
    Bocti, C.
    Fulop, T.
    Paquet, N.
    Cunnane, S. C.
    [J]. EXPERIMENTAL GERONTOLOGY, 2018, 107 : 18 - 26
  • [15] Alzheimer's disease drug development pipeline: 2019
    Cummings, Jeffrey
    Lee, Garam
    Ritter, Aaron
    Sabbagh, Marwan
    Zhong, Kate
    [J]. ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS, 2019, 5 (01) : 272 - 293
  • [16] SHORT CHAIN FATTY-ACIDS IN HUMAN LARGE-INTESTINE, PORTAL, HEPATIC AND VENOUS-BLOOD
    CUMMINGS, JH
    POMARE, EW
    BRANCH, WJ
    NAYLOR, CPE
    MACFARLANE, GT
    [J]. GUT, 1987, 28 (10) : 1221 - 1227
  • [17] Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing
    Cunnane, Stephen C.
    Trushina, Eugenia
    Morland, Cecilie
    Prigione, Alessandro
    Casadesus, Gemma
    Andrews, Zane B.
    Beal, M. Flint
    Bergersen, Linda H.
    Brinton, Roberta D.
    de la Monte, Suzanne
    Eckert, Anne
    Harvey, Jenni
    Jeggo, Ross
    Jhamandas, Jack H.
    Kann, Oliver
    la Cour, Clothide Mannoury
    Martin, William F.
    Mithieux, Gilles
    Moreira, Paula, I
    Murphy, Michael P.
    Nave, Klaus-Armin
    Nuriel, Tal
    Oliet, Stephane H. R.
    Saudou, Frederic
    Mattson, Mark P.
    Swerdlow, Russell H.
    Millan, Mark J.
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2020, 19 (09) : 609 - 633
  • [18] Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer's Disease
    Cunnane, Stephen C.
    Courchesne-Loyer, Alexandre
    Vandenberghe, Camille
    St-Pierre, Valerie
    Fortier, Melanie
    Hennebelle, Marie
    Croteau, Etienne
    Bocti, Christian
    Fulop, Tamas
    Castellano, Christian-Alexandre
    [J]. FRONTIERS IN MOLECULAR NEUROSCIENCE, 2016, 9
  • [19] The role of short-chain fatty acids in microbiota-gut-brain communication
    Dalile, Boushra
    Van Oudenhove, Lukas
    Vervliet, Bram
    Verbeke, Kristin
    [J]. NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2019, 16 (08) : 461 - 478
  • [20] Type 3 diabetes is sporadic Alzheimer's disease: Mini-review
    de la Monte, Suzanne M.
    [J]. EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2014, 24 (12) : 1954 - 1960