Promotion of astrocyte-neuron glutamate-glutamine shuttle by SCFA contributes to the alleviation of Alzheimer's disease
Open accessAbstract
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 neuroprotective 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 Aβ 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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Probiotic and prebiotic interventions aimed at elevating SCFA levels have neuroprotective effects in AD mouse models by inhibiting glial activation and Aβ deposition.
“Moreover, probiotic and prebiotic interventions aimed at elevating SCFA levels have demonstrated neuroprotective effects in AD mouse models by inhibiting glial activation and Aβ deposition.301–306”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [306]
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
- Authors
- Sun, Y., Zhang, H., Zhang, X., Wang, W., Chen, Y., Cai, Z., Wang, Q., Wang, J., & Shi, Y.
- Affiliations
- Chinese Academy of Sciences (CN)
- University of Chinese Academy of Sciences (CN)
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2023-06
- Volume
- 62
- Pages
- 102690
- ISSN
- 2213-2317 (ISSN-L)
- PMC
- PMC10122027
- OpenAlex
- W4360999445
- Cited by
- 151
- References
- 59
- Citations by year
- 2026: 42 · 2025: 63 · 2024: 37 · 2023: 9
- FWCI
- 26.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Redox Biology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Chinese Academy of Sciences (XDB29010000, XDB29020000)
- Youth Innovation Promotion Association of the Chinese Academy of Sciences (Y201921)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- short-chain fatty acids, Alzheimer's disease, astrocyte-neuron communication, oxidative stress, neuroenergetics, gut microbiota, dietary supplementation, APP/PS1 mice, amyloid-beta deposition, tau hyperphosphorylation, cognitive impairment, hippocampus, neuroprotection
- MeSH terms
- Alzheimer Disease, Animals, Astrocytes, Disease Models, Animal, Glutamates, Glutamine, Mice, Transgenic, Neurons, Amyloid beta-Peptides, Mice
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