Sodium butyrate ameliorates the impairment of synaptic plasticity by inhibiting the neuroinflammation in 5XFAD mice
Abstract
Current strategies for the treatment of Alzheimer's disease (AD) focus on the pathology in the later stages of disease progression. Early microglia abnormality and β-amyloid (Aβ) deposition trigger disease development before identical symptoms emerge, which leads to poor clinical treatment effects in the later stages. In the early stage of disease progression, microglia in brains of 5XFAD mice have been activated by Aβ plaques to secrete more pro-inflammatory cytokines. In the meantime, these cytokines up-regulate Aβ via increasing the APP processing. Sodium butyrate (NaB), as one of the short chain fatty acid (SCFA) generated by gut microbiota, is the inhibitor of histone deacetylase (HDAC), which reduces the secretion of pro-inflammatory cytokines. In our experiment, 8-week-old 5XFAD mice and their litter WT mice were treated with NaB or normal saline for 2 weeks (WT + Vehicle group, WT + NaB group, AD + Vehicle group and AD + NaB group). After treatment, behavioral tests were carried out. The novel object recognition (NOR) and Morris water maze (MWM) tests demonstrated that there was no significant difference between four groups of mice. The results of long-term potentiation (LTP) and depotentiation (DEP) illustrated that the synaptic plasticity was promoted in 5XFAD mice after treatment with NaB. Compared to the AD + Vehicle group, the dendritic spines were more abundant in other groups of mice. Furthermore, the synapse-associated proteins (PSD-95, SYP, NR2B) were reduced and the pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) were increased in the AD + Vehicle group. These phenomena were reversed after treatment with NaB. Moreover, our results suggested that NaB suppressed the over-activation of microglia and the accumulation of Aβ in AD mice. Altogether, all results illustrated that HDAC inhibitor NaB could ameliorate the synaptic plasticity by reducing neuroinflammation in 5XFAD mice in the early stage of the disease.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Sodium butyrate has neuroprotective effects in 5xFAD mice by inhibiting microglial activation and promoting synaptic plasticity.
“Studies have demonstrated the neuroprotective effects of sodium butyrate in 5xFAD mice by inhibiting microglial activation and promoting synaptic plasticity (Fig. 3a).299,300”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [300]
Cites
The chemokine system in diverse forms of macrophage activation and polarization
MANTOVANI, A., SICA, A., SOZZANI, S., ALLAVENA, P., VECCHI, A., & LOCATI, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.09.015 · Cited by 6,534 · see citing works
Morris water maze: procedures for assessing spatial and related forms of learning and memory
Vorhees, C. V., & Williams, M. T. (2006) · Nature Protocols · doi:10.1038/nprot.2006.116 · Cited by 4,629 · see citing works
Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease
Sampson, T. R., Debelius, J. W., Thron, T., Janssen, S., Shastri, G. G., Ilhan, Z. E., Challis, C., Schretter, C. E., Rocha, S., Gradinaru, V., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.018 · Cited by 3,622 · see citing works
Host microbiota constantly control maturation and function of microglia in the CNS
Erny, D., Hrabě de Angelis, A. L., Jaitin, D., Wieghofer, P., Staszewski, O., David, E., Keren-Shaul, H., Mahlakoiv, T., Jakobshagen, K., Buch, T., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4030 · Cited by 3,569 · see citing works
Oakley, H., Cole, S. L., Logan, S., Maus, E., Shao, P., Craft, J., Guillozet-Bongaarts, A., Ohno, M., Disterhoft, J., Van Eldik, L., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1202-06.2006 · Cited by 3,530 · see citing works
Integrating cell-signalling pathways with NF-κB and IKK function
Perkins, N. D. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2083 · Cited by 2,350 · see citing works
Introduction to NF-κB: players, pathways, perspectives
Gilmore, T. D. (2006) · Oncogene · doi:10.1038/sj.onc.1209954 · Cited by 2,227 · see citing works
Microglial physiology: unique stimuli, specialized responses
Ransohoff, R. M., & Perry, V. H. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132528 · Cited by 1,858 · see citing works
Hu, X.-M., Li, P.-Y., Guo, Y., Wang, H., Leak, R., Chen, S., Gao, Y.-Q., & Chen, J. (2012) · Stroke · doi:10.1161/strokeaha.112.659656 · Cited by 1,445 · see citing works
Object recognition test in mice
Leger, M., Quiedeville, A., Bouet, V., Haelewyn, B., Boulouard, M., Schumann-Bard, P., & Freret, T. (2013) · Nature Protocols · doi:10.1038/nprot.2013.155 · Cited by 1,357 · see citing works
Role of pro-inflammatory cytokines released from microglia in Alzheimer's disease.
(2015) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2305-5839.2015.03.49 · Cited by 1,288 · see citing works
Regulation of tumour necrosis factor signalling: live or let die
Brenner, D., Blaser, H., & Mak, T. W. (2015) · Nature Reviews Immunology · doi:10.1038/nri3834 · Cited by 998 · see citing works
Inflammation in Alzheimer Disease--A Brief Review of the Basic Science and Clinical Literature
Wyss-Coray, T., & Rogers, J. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006346 · Cited by 975 · see citing works
Ferrante, R. J., Kubilus, J. K., Lee, J.-H., Ryu, H., Beesen, A. A., Zucker, B., Smith, K., Kowall, N. W., Ratan, R. R., Luthi‐Carter, R., et al. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-28-09418.2003 · Cited by 694 · see citing works
A method for vibratome sectioning of Golgi–Cox stained whole rat brain
Gibb, R. L., & Kolb, B. E. (1998) · Journal of Neuroscience Methods · doi:10.1016/s0165-0270(97)00163-5 · Cited by 618 · see citing works
CLINICAL DEVELOPMENT OF HISTONE DEACETYLASE INHIBITORS AS ANTICANCER AGENTS
Drummond, D. C., Noble, C. O., Kirpotin, D. B., Guo, Z., Scott, G. K., & Benz, C. C. (2004) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.45.120403.095825 · Cited by 598 · see citing works
CD14 and Toll-Like Receptors 2 and 4 Are Required for Fibrillar Aβ-Stimulated Microglial Activation
Reed-Geaghan, E. G., Savage, J. C., Hise, A. G., & Landreth, G. E. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3158-09.2009 · Cited by 591 · see citing works
Kim, H. J., Rowe, M. K., Ren, M., Hong, J., Chen, P.-S., & Chuang, D. (2007) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.120188 · Cited by 557 · see citing works
Intestinal dysbiosis and lowered serum lipopolysaccharide-binding protein in Parkinson's disease
Hasegawa, S., Goto, S., Tsuji, H., Okuno, T., Asahara, T., Nomoto, K., Shibata, A., Fujisawa, Y., Minato, T., Okamoto, A., et al. (2015) · PLOS ONE · doi:10.1371/journal.pone.0142164 · Cited by 523 · see citing works
Understanding and exploiting the endogenous interleukin-10/STAT3-mediated anti-inflammatory response
MURRAY, P. (2006) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2006.01.010 · Cited by 436 · see citing works
Eimer, W. A., & Vassar, R. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-2 · Cited by 425 · see citing works
Williams, L. M., Bradley, L., Smith, A. J., & Foxwell, B. M. J. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.1.567 · Cited by 394 · see citing works
Progressive age‐related development of Alzheimer‐like pathology in APP/PS1 mice
Trinchese, F., Liu, S., Battaglia, F., Walter, S., Mathews, P. M., & Arancio, O. (2004) · Annals of Neurology · doi:10.1002/ana.20101 · Cited by 369 · see citing works
Blasko, I., Marx, F., Steiner, E., Hartmann, T., & Grubeck-Loebenstein, B. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.1.63 · Cited by 278 · see citing works
Patnala, R., Arumugam, T. V., Gupta, N., & Dheen, S. T. (2017) · Molecular Neurobiology · doi:10.1007/s12035-016-0149-z · Cited by 278 · see citing works
Pro-inflammatory cytokines and their effects in the dentate gyrus
Pickering, M., & O’Connor, J. J. (2007) · Progress in Brain Research · doi:10.1016/s0079-6123(07)63020-9 · Cited by 217 · see citing works
Przanowski, P., Dąbrowski, M., Ellert‐Miklaszewska, A., Kloss, M., Mieczkowski, J., Kaza, B., Ronowicz, A., Hu, F., Piotrowski, A., Kettenmann, H., et al. (2013) · Journal of Molecular Medicine · doi:10.1007/s00109-013-1090-5 · Cited by 186 · see citing works
Takata, K., Kitamura, Y., Saeki, M., Terada, M., Kagitani, S., Kitamura, R., Fujikawa, Y., Maelicke, A., Tomimoto, H., Taniguchi, T., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.142356 · Cited by 176 · see citing works
Egorin, M. J., Yuan, Z.-M., Sentz, D. L., Plaisance, K. I., & Eiseman, J. L. (1999) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s002800050922 · Cited by 166 · see citing works
Fernando, W. M. A. D. B., Martins, I. J., Morici, M., Bharadwaj, P., Rainey-Smith, S. R., Lim, W. L. F., & Martins, R. N. (2020) · Journal of Alzheimer's Disease · doi:10.3233/jad-190120 · Cited by 164 · see citing works
Lü, Y., Guo, Z., Zhang, Y., Li, C., Zhang, Y., Guo, Q., Chen, Q., Chen, X., He, X., Liu, L., et al. (2018) · Advanced Science · doi:10.1002/advs.201801586 · Cited by 162 · see citing works
β-Amyloid and the Pathomechanisms of Alzheimer’s Disease: A Comprehensive View
Penke, B., Bogár, F., & Fülöp, L. (2017) · Molecules · doi:10.3390/molecules22101692 · Cited by 135 · see citing works
Tobinick, E. (2009) · CNS Drugs · doi:10.2165/11310810-000000000-00000 · Cited by 117 · see citing works
Normal induction but accelerated decay of LTP in APP + PS1 transgenic mice
Gureviciene, I., Ikonen, S., Gurevicius, K., Sarkaki, A., Groen, T. V., Pussinen, R., Ylinen, A., & Tanila, H. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2003.11.011 · Cited by 115 · see citing works
Wu, X. G., Lv, Y., Du, Y., Chen, F., Reed, M. N., Hu, M. Y., Suppiramaniam, V. D., Tang, S., & Hong, H. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.06.018 · Cited by 100 · see citing works
Jaworska, J., Zalewska, T., Sypecka, J., & Ziemka‐Nałęcz, M. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-1518-1 · Cited by 94 · see citing works
Barrett, J. P., Henry, R. J., Villapol, S., Stoica, B. A., Kumar, A., Burns, M. P., Faden, A. I., & Loane, D. J. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0843-4 · Cited by 91 · see citing works
Faustino, C. M. C., Rijo, P. M., & Reis, C. P. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.03.020 · Cited by 82 · see citing works
IL-10 promotes survival of microglia without activating Akt
Strle, K., Zhou, J.-H., Broussard, S. R., Venters, H., Johnson, R. W., Freund, G. G., Dantzer, R., & Kelley, K. W. (2002) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(01)00444-1 · Cited by 76 · see citing works
Stopping Alzheimer's Before It Starts
Miller, G. (2012) · Science · doi:10.1126/science.337.6096.790 · Cited by 73 · see citing works
Zou, C., Shi, Y., Ohli, J., Schüller, U., Dorostkar, M. M., & Herms, J. W. (2016) · Acta Neuropathologica · doi:10.1007/s00401-015-1527-8 · Cited by 66 · see citing works
Paouri, E., Tzara, O., Zenelak, S., & Georgopoulos, S. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170065 · Cited by 60 · see citing works
Chistyakov, D. V., Azbukina, N. V., Astakhova, A. A., Goriainov, S. V., Chistyakov, V. V., & Sergeeva, M. G. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19092793 · Cited by 52 · see citing works
Graphene oxide enhances β-amyloid clearance by inducing autophagy of microglia and neurons
Li, X., Li, K., Chu, F., Huang, J., & Yang, Z. R. (2020) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2020.109126 · Cited by 52 · see citing works
Self-citationZhang, L., Zhou, Z., Zhai, W., Pang, J., Mo, Y., Yang, G., Qu, Z., & Hu, Y. (2019) · Metabolic Brain Disease · doi:10.1007/s11011-019-00398-0 · Cited by 41 · see citing works
Regulation of synaptic plasticity by mGluR1 studied in vivo in mGluR1 mutant mice
Bordi, F., Reggiani, A. M., & Conquet, F. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00320-x · Cited by 35 · see citing works
Fujikura, M., Iwahara, N., Hisahara, S., Kawamata, J., Matsumura, A., Yokokawa, K., Saito, T., Manabe, T., Matsushita, T., Suzuki, S., et al. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-180904 · Cited by 35 · see citing works
Kao, A. C.-C., Chan, K. W., Anthony, D. C., Lennox, B. R., & Burnet, P. W. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.02.014 · Cited by 32 · see citing works
Filgueiras, L. R., Brandt, S. L., Ramalho, T. R. D. O., Jancar, S., & Serezani, C. H. (2016) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2016.08.001 · Cited by 29 · see citing works
Reisi, P., Zarei, G., Alaei, H., & Javanmard, S. (2014) · Advanced Biomedical Research · doi:10.4103/2277-9175.142044 · Cited by 18 · see citing works
Shen, H., Pan, X., Zhang, J., Zeng, Y., Zhou, M., Yang, L., Ye, B., Dai, X., Zhu, Y., & Chen, X. (2016) · Chinese Medical Journal · doi:10.4103/0366-6999.194643 · Cited by 17 · see citing works
Hottman, D. A., Cheng, S., Gram, A., LeBlanc, K. J., Yuan, L., & Li, L. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2018.01.026 · Cited by 17 · see citing works
Differential expression of HDAC and HAT genes in atrophying skeletal muscle
Beharry, A. W., & Judge, A. R. (2015) · Muscle & Nerve · doi:10.1002/mus.24912 · Cited by 16 · see citing works
Effect of dihydrotestosterone on gastrointestinal tract of male Alzheimer's disease transgenic mice.
Karri, S., Acosta‐Martínez, V., & Coimbatore, G. (2010) · PubMed · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
Chen, Y., Xu, J., & Chen, Y. (2021) · Nutrients · doi:10.3390/nu13062099 · Cited by 917 · see citing works
“In addition, the advance of molecular technologies including in vitro bacterial culture system [19], in vitro primary intestinal cell culture system [13], and in vivo studies in animal models [20,21] offers great opportunities to study the effects of specific bacterial taxa and their metabolites on the pathogenesis of…”
BackgroundNey, L.-M., Wipplinger, M., Grossmann, M., Engert, N., Wegner, V. D., & Mosig, A. S. (2023) · Open Biology · doi:10.1098/rsob.230014 · Cited by 338 · see citing works
Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease
Bairamian, D., Sha, S., Rolhion, N., Sokol, H., Dorothée, G., Lemere, C. A., & Krantic, S. M. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00522-2 · Cited by 318 · see citing works
“sodium-butyrate) could ameliorate synaptic impairments at 2 months of age (corresponding to the pre-symptomatic stage in 5xFAD mice) via inhibition of neuroinflammation [77] which is in line with anti-inflammatory potential of SCFAs in “successful” aging [104] but contrasts pro-inflammatory effects of SCFAs in PD [125…”
BackgroundCurrent understanding of the Alzheimer’s disease-associated microbiome and therapeutic strategies
Seo, D.-O., & Holtzman, D. M. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-023-01146-2 · Cited by 249 · see citing works
“Even within the AD fi eld, the effects of SCFAs are not always consistent, as some literature indicates that one SCFA supplement, sodium butyrate, alleviates A β deposition 69,70 .”
BackgroundMechanisms of Short-Chain Fatty Acids Derived from Gut Microbiota in Alzheimer's Disease
Qian, X., Xie, R.-Y., Liu, X., Chen, S., & Tang, H. (2022) · Aging and Disease · doi:10.14336/ad.2021.1215 · Cited by 219 · see citing works
Short-chain fatty acid: An updated review on signaling, metabolism, and therapeutic effects
Rekha, K., Venkidasamy, B., Samynathan, R., Nagella, P., Ребезов, М. Б., Khayrullin, M., Ponomarev, E., Bouyahya, A., Sarkar, T., Shariati, M. A., et al. (2022) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2022.2124231 · Cited by 169 · see citing works
Sun, Y., Zhang, H., Zhang, X., Wang, W., Chen, Y., Cai, Z., Wang, Q., Wang, J., & Shi, Y. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102690 · Cited by 151 · see citing works
Gut microbiome-targeted therapies for Alzheimer’s disease
Zhang, T., Gao, G., Kwok, L., & Sun, Z. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2271613 · Cited by 156 · see citing works
“65 In addition, LPS, pro-inflammatory compounds produced by Gram-negative bacterial membranes, could also lead to amyloid and tau pathology in animal models.”
BackgroundSalminen, A. (2023) · Journal of Molecular Medicine · doi:10.1007/s00109-023-02289-5 · Cited by 149 · see citing works
Cao, Q., Shen, M., Li, R., Liu, Y., Zeng, Z., Zhou, J., Niu, D., Zhang, Q., Wang, R., Yao, J., et al. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03454-y · Cited by 129 · see citing works
“In vivo experiments showed that butyrate treatment suppressed excessive activation of microglia in 5×FAD mice, reduced pro-inflammatory cytokines and Aβ levels, and enhanced synaptic plasticity and expression of synaptic proteins (e.g., PSD-95, SYP, NR2B) [101].”
Pan, R.-Y., Zhang, J., Wang, J., Wang, Y., Li, Z., Liao, Y., Liao, Y., Zhang, C., Liu, Z., Song, L., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00311-y · Cited by 107 · see citing works
Multiple roles of short-chain fatty acids in Alzheimer disease
Chen, H., Meng, L., & Shen, L. (2021) · Nutrition · doi:10.1016/j.nut.2021.111499 · Cited by 107 · see citing works
Impact of Contaminants on Microbiota: Linking the Gut–Brain Axis with Neurotoxicity
Balaguer-Trias, J., Deepika, D., Schuhmacher, M., & Kumar, V. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19031368 · Cited by 91 · see citing works
“Faecalibacterium prausnitzii and Roseburia are the main SCFAs-producing bacteria; specifically, they are producers of butyrate.”
BackgroundInfluentialTherapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside
Ma, Y., Li, X., Yu, J., & Wang, Y. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00404-1 · Cited by 87 · see citing works
“Sodium butyrate has been observed to enhance the long-term potentiation and depotentiation, and promote the development of dendritic spines and synapse-associated proteins in 5 × FAD mice [144].”
BackgroundSelf-citationThe gut microbiome and Alzheimer’s disease: Complex and bidirectional interactions
Tarawneh, R. M., & Penhos, E. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104814 · Cited by 89 · see citing works
Majumdar, A., Venkatesh, I. P. S., & Basu, A. (2023) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.2c00803 · Cited by 85 · see citing works
Dong, T. S., & Mayer, E. A. (2024) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2024.01.024 · Cited by 84 · see citing works
“33 For example, butyrate has been shown to promote neuronal growth, 34 enhance synaptic plasticity, 35 and inhibit immune responses in the gut and brain.”
BackgroundThe Gut Microbiome as a Regulator of the Neuroimmune Landscape
Yu, L. W., Agirman, G., & Hsiao, E. Y. (2022) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101320-014237 · Cited by 75 · see citing works
Role of histone deacetylases and their inhibitors in neurological diseases
Zhang, L.-Y., Zhang, S.-Y., Wen, R., Zhang, T.-N., & Yang, N. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107410 · Cited by 84 · see citing works
Zhou, Y., Xie, L., Schröder, J., Schuster, I. S., Nakai, M. E., Sun, G., Sun, Y., Mariño, E., Degli‐Esposti, M. A., Marques, F. Z., et al. (2023) · Journal of Neuroscience · doi:10.1523/jneurosci.0724-23.2023 · Cited by 79 · see citing works
Wang, C., Zheng, D., Weng, F., Jin, Y., & He, L. (2021) · Psychopharmacology · doi:10.1007/s00213-021-06025-0 · Cited by 76 · see citing works
Fasina, O. B., Wang, J., Mo, J., Osada, H., Ohno, H., Pan, W., Xiang, L., & Qi, J. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.814271 · Cited by 76 · see citing works
Cuervo-Zanatta, D., Syeda, T., Sánchez-Valle, V., Irene-Fierro, M., Torres‐Aguilar, P. C., Torres-Ramos, M., Shibayama-Salas, M., Silva-Olivares, A., Noriega, L. G., Torres, N., et al. (2022) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-022-01268-7 · Cited by 75 · see citing works
Short-chain fatty acids: Important components of the gut-brain axis against AD
Huang, Y., Wang, Y. F., Miao, J., Zheng, R. F., & Li, J. Y. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116601 · Cited by 70 · see citing works
Hsu, C., Khachatryan, L., Younis, N. K., Mustafa, M. A., Ahmad, N., Athab, Z. H., Валерьевна, П. А., Викторовна, К. Е., Mirzaei, R., & Karampoor, S. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1456793 · Cited by 68 · see citing works
Su, S., Chen, M., Wu, Y., Lin, Q. D., Wang, D., Sun, J., & Hai, J. (2023) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14089 · Cited by 57 · see citing works
Targeting gut microbiota to alleviate neuroinflammation in Alzheimer’s disease
Nguyen, V. T. T., & Endres, K. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114418 · Cited by 52 · see citing works
The role of microglia in Alzheimer's disease and progress of treatment
Guan, Y.-H., Zhang, L.-W., Wang, S.-Y., Deng, Y.-D., Zhou, H.-S., Chen, D., & Zhang, L. (2022) · Ibrain · doi:10.1002/ibra.12023 · Cited by 48 · see citing works
Cristiano, C., Cuozzo, M., Coretti, L., Liguori, F. M., Cimmino, F., Turco, L., Avagliano, C., Aviello, G., Mollica, M. P., Lembo, F., et al. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113528 · Cited by 52 · see citing works
Gut microbial metabolism in Alzheimer's disease and related dementias
Kang, J. W., Vemuganti, V., Kuehn, J. F., Ulland, T. K., Rey, F. E., & Bendlin, B. B. (2024) · Neurotherapeutics · doi:10.1016/j.neurot.2024.e00470 · Cited by 49 · see citing works
Cavaliere, G., Catapano, A., Trinchese, G., Cimmino, F., Penna, E., Pizzella, A., Cristiano, C., Lama, A., Crispino, M., & Mollica, M. P. (2022) · Antioxidants · doi:10.3390/antiox12010004 · Cited by 52 · see citing works
“Interestingly, butyrate was showed to relieve neuroinflammation and enhance synaptic plasticity in 5XFAD mice, a transgenic mouse model of AD, suggesting a protective role of butyrate in this pathology [20].”
Lee, B., Lee, S. M., Song, J. W., & Choi, J. W. (2024) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2024.009 · Cited by 48 · see citing works
Microglia and gut microbiota: A double-edged sword in Alzheimer's disease
Bano, N., Khan, S., Ahamad, S., Kanshana, J. S., Dar, N. J., Khan, S. J., Nazir, A., & Bhat, S. A. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102515 · Cited by 49 · see citing works
The complex relationship between gut microbiota and Alzheimer’s disease: A systematic review
Zhou, X.-P., Sun, L.-B., Liu, W., Zhu, W.-M., Li, L.-C., Song, X., Xing, J.-P., & Gao, S. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102637 · Cited by 50 · see citing works
“Jiang et al. reported that sodium butyrate suppressed excessive microglial activation and A β accumulation in AD mice (Jiang et al., 2021).”
Qu, L., Li, Y., Liu, F., Fang, Y., He, J., Ma, J., Xu, T., Wang, L., Lei, P., Dong, H., et al. (2023) · Aging and Disease · doi:10.14336/ad.2023.0823-2 · Cited by 46 · see citing works
“Sodium butyrate mitigates radiation-induced cognitive impairment by mitigates inhibiting hippocampal phosphorylation of cAMP response element binding proteins or promoting the expression of brain derived neurotrophic factor (BDNF) [40].”
BackgroundFunctional effects of gut microbiota-derived metabolites in Alzheimer's disease
Choi, H., & Mook‐Jung, I. (2023) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2023.102730 · Cited by 41 · see citing works
Prajapati, S. K., Shah, R., Alford, N., Mishra, S. P., Jain, S., HANSEN, B. C., Sanberg, P. R., Molina, A. J. A., & Yadav, H. (2023) · The Journals of Gerontology Series A · doi:10.1093/gerona/glad226 · Cited by 42 · see citing works
Bashir, B., Gulati, M., Vishwas, S., Gupta, G., Dhanasekaran, M., Paudel, K. R., Chellappan, D. K., Anand, K., Negi, P., Singh, P. K., et al. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102689 · Cited by 43 · see citing works
Andrade-Talavera, Y., & Rodríguez-Moreno, A. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.696476 · Cited by 39 · see citing works
Butyrate as a potential therapeutic agent for neurodegenerative disorders
Chakraborty, P., Gamage, H. K. A. H., & Laird, A. S. (2024) · Neurochemistry International · doi:10.1016/j.neuint.2024.105745 · Cited by 41 · see citing works
Catumbela, C. S. G., Giridharan, V. V., Barichello, T., & Morales, R. (2023) · Translational Neurodegeneration · doi:10.1186/s40035-023-00369-7 · Cited by 37 · see citing works
“Of note, butyrate is a short-chain fatty acid (SCFA) associated with neuroprotective properties in experimental models of AD [128], Parkinson’s disease [129], spinal cord injury [130], and neuropathic pain [131].”
BackgroundZhang, S., Wu, Z., Zhang, S., Ru, Y., Wang, Q., Tong, H., Qin, Q., Yan, Q., Li, Z., & Wu, G. (2025) · Food & Function · doi:10.1039/d5fo03139g · Cited by 37 · see citing works
Wang, X., Sun, Z., Yang, T., Lin, F. H., Ye, S., Yan, J., Li, T., & Chen, J. (2023) · mSystems · doi:10.1128/msystems.00415-23 · Cited by 36 · see citing works
“Previous studies also showed that butyric acid treatment actively modulated synaptic plasticity, induced broad neurotransmitter gene expression, and alleviated behavioral abnormalities (40, 43, 44).”
ResultNanomedicines for Alzheimer's disease: Therapies based on pathological mechanisms
Cheng, G., Xie, A., Yan, Z., Zhu, X., Song, Y., & Chen, T. (2023) · Brain‐X · doi:10.1002/brx2.27 · Cited by 35 · see citing works
Psychobiotics for Mitigation of Neuro‐Degenerative Diseases: Recent Advancements
Dhyani, P., Goyal, C., Dhull, S. B., Chauhan, A. K., Saharan, B. S., Harshita, Duhan, J. S., & Gökşen, G. (2023) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202300461 · Cited by 30 · see citing works
Microglial cells: Sensors for neuronal activity and microbiota-derived molecules
D’Alessandro, G., Marrocco, F., & Limatola, C. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1011129 · Cited by 30 · see citing works
Zhan, Y., Al‐Nusaif, M., Ding, C., Zhao, L., & Dong, C. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1130730 · Cited by 30 · see citing works
“Gut microbiome may lead to increased neuroinflammation and decreased synaptic plasticity, both of which are thought to contribute to the development and progression of AD (Jiang et al., 2021).”
BackgroundAmeen, A. O., Freude, K., & Aldana, B. I. (2022) · Biomedicines · doi:10.3390/biomedicines10112778 · Cited by 28 · see citing works
HDACs in the Brain: From Chromatin Remodeling to Neurodegenerative Disease
Diniz, L. P., Pinheiro, P. D. S. M., Franco, L. S., & Gomes, F. C. A. (2025) · Cells · doi:10.3390/cells14171338 · Cited by 26 · see citing works
“In the 5XFAD mouse model of AD, sodium butyrate treatment also improved synaptic plasticity, increased dendritic spine density, and reversed disease-associated reductions in synaptic proteins and increases in pro-inflammatory cytokines [72].”
Wang, J., Fasina, O. B., Manzoor, M., Wang, Y., Liu, Q., Mo, J., Ohno, H., Osada, H., Xiang, L., & Qi, J. (2023) · Phytomedicine · doi:10.1016/j.phymed.2023.154730 · Cited by 26 · see citing works
Yoshikawa, S., Taniguchi, K., Sawamura, H., Ikeda, Y., Tsuji, A., & Matsuda, S. (2022) · Metabolites · doi:10.3390/metabo12111052 · Cited by 25 · see citing works
Wang, L., Lu, Y., Liu, J., Wang, S., Fei, Z., Zhang, K., Zhang, D., & Jin, X. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.155394 · Cited by 24 · see citing works
Li, C. P. I., Fan, Y., & Chen, X. (2026) · npj Biofilms and Microbiomes · doi:10.1038/s41522-026-00912-0 · Cited by 24 · see citing works
Therapeutic Strategies Aimed at Improving Neuroplasticity in Alzheimer Disease
Colavitta, M. F., & Barrantes, F. J. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15082052 · Cited by 25 · see citing works
Li, X., Huang, L., Kong, L.-L., Su, Y., Zhou, H.-L., Ji, P., Sun, R., Wang, C., Li, W., & Li, W.-Z. (2022) · Molecular Medicine Reports · doi:10.3892/mmr.2022.12893 · Cited by 24 · see citing works
“Furthermore, overexpression of these cytokines contributes to synaptic plasticity dysfunction and neuronal damages in 5xFad mice (56).”
Self-citationKumari, E., Xu, A., Chen, R., Yan, Y., Yang, Z. R., & Zhang, T. (2022) · Experimental Neurology · doi:10.1016/j.expneurol.2022.114231 · Cited by 21 · see citing works
Self-citationMicrobiome influences on neuro-immune interactions in neurodegenerative disease
Menees, K. B., Otero, B. A., & Tansey, M. G. (2022) · International review of neurobiology · doi:10.1016/bs.irn.2022.07.006 · Cited by 23 · see citing works
Zhang, Y., Ma, R., Wang, W., Deng, Q., Cao, C., Yu, C., Li, S., Shi, L., & Tian, J. (2023) · Experimental Gerontology · doi:10.1016/j.exger.2023.112139 · Cited by 20 · see citing works
Brain-Gut and Microbiota-Gut-Brain Communication in Type-2 Diabetes Linked Alzheimer’s Disease
Momen, Y. S., Mishra, J., & Kumar, N. (2024) · Nutrients · doi:10.3390/nu16152558 · Cited by 24 · see citing works
“This epigenetic alteration has the potential to amplify the activation of genes linked to synaptic plasticity and the sustenance of neurons, thereby inducing cognitive improvement in APP/PS1 and 5XFAD AD mice models [76–79].”
Exogenous Short Chain Fatty Acid Effects in APP/PS1 Mice
Zajac, D. J., Shaw, B. C., Braun, D. J., Green, S. J., Morganti, J. M., & Estus, S. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.873549 · Cited by 21 · see citing works
Butyrate promotes post-stroke outcomes in aged mice via interleukin-22
Chen, Z., Xin, L., Yang, L., Xu, M., Li, F. Y., Zhou, M., & Yan, T. (2023) · Experimental Neurology · doi:10.1016/j.expneurol.2023.114351 · Cited by 20 · see citing works
Gut microbiota metabolites: potential therapeutic targets for Alzheimer’s disease?
Zhang, S., Lu, J., Jin, Z., Xu, H., Zhang, D., Chen, J., & Wang, J. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1459655 · Cited by 24 · see citing works
Zhang, Y., Huang, Q., Wang, S., Liao, Z., Jin, H., Huang, S., Hong, X., Liu, Y., Pang, J., Shen, Q., et al. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.814432 · Cited by 19 · see citing works
“According to research, increasing Aβ oligomer formation triggers neuronal dysfunction and network alternations in learning and memory circuitry prior to the clinical onset of AD, and inhibition of Aβ accumulation improves cognitive behaviour and neuroinflammation in AD mice (Jiang et al., 2021).”
BackgroundAl-Adham, I. S. I., Agha, A. S. A. A., Al‐Akayleh, F., Al-Remawi, M. M., Jaber, N., Al-Manasur, M. A., & Collier, P. J. (2025) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-025-10465-x · Cited by 19 · see citing works
“…(mucin 2), sIgA (secretory immunoglobulin A), BMD (bone mineral density), BMC (bone mineral content), and TRACP-5b (tartrate-resistant acid phosphatase 5b) neuroinflammation leads to a decrease in amyloid-beta (Aβ) plaques and improved cognitive performance in the early stages of the disease [76].”
Churchward, M. A., Michaud, E. R., Mullish, B. H., Blanco, J. M., Perez, I. G., Marchesi, J. R., Xu, H., Kao, D. H., & Todd, K. G. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e16908 · Cited by 19 · see citing works
Butyrate: a key mediator of gut-brain communication in Alzheimer’s disease
Kachoueiyan, F., Kalkhoran, N. Y., Kalkhoran, A. Y., Kyada, A., Rekha, M. M., Chaudhary, K., Barwal, A., Sead, F. F., & Joshi, K. K. (2025) · Metabolic Brain Disease · doi:10.1007/s11011-025-01617-7 · Cited by 17 · see citing works
“Previous research has demonstrated that SB administration reduces Aβ levels while improving cognitive function (Sun et al. 2020a, b ; Govindarajan et al. 2011 ; Fernando et al. 2020 ; Jiang et al. 2021 ).”
Microbial Metabolomes in Alzheimer’s Disease: From Pathogenesis to Therapeutic Potential
Borrego-Ruiz, A., & Borrego, J. J. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47090724 · Cited by 20 · see citing works
“Preclinical studies have demonstrated that butyrate positively influences synaptic plasticity by increasing synapse-associated proteins and facilitating long-term potentiation and depotentiation [164].”
The gut–brain axis in Alzheimer’s disease: how gut microbiota modulate microglial function
Wang, H., Yang, F., Gao, Z., Cheng, Z.-D., & Liang, X. (2025) · Frontiers in Aging · doi:10.3389/fragi.2025.1704047 · Cited by 21 · see citing works
“Butyrate, a butyrate salt derived from SCFAs, reduces the secretion of pro-inflammatory cytokines by inhibiting histone deacetylase (HDAC), thereby suppressing the overactivation of microglia and the accumulation of A β and improving synaptic plasticity (Jiang et al., 2021).”
Brossaud, R., Oullier, T., Bessard, A., Aubert, P., Brossard, L., Mahé, M. M., Caillaud, M., Delfino, G., Paillusson, S., Falentin, H., et al. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03522-6 · Cited by 19 · see citing works
Liu, J., Hui, A., Wang, J., Hu, Q., Li, S., Chen, Y., Wu, Z., & Zhang, W. (2023) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2023.110675 · Cited by 17 · see citing works
Ullah, R., Ali, G., Subhan, F., Khan, A., Halim, S. A., Naveed, M., Kalsoom, S., & Al-Harrasi, A. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.108083 · Cited by 17 · see citing works
Sodium Butyrate Protects Against Ethanol-Induced Toxicity in SH-SY5Y Cell Line
Getachew, B., Csoka, A. B., Garden, A. R., Copeland, R., & Tizabi, Y. (2021) · Neurotoxicity Research · doi:10.1007/s12640-021-00418-x · Cited by 17 · see citing works
Kang, X., Cheng, E., Guo, P., Xi, L., Xiang, C., Xu, S., Zhang, Y., Yang, Y., Zhang, J. J., & Long, H. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.157009 · Cited by 16 · see citing works
A high‐salt diet induces synaptic loss and memory impairment via gut microbiota and butyrate in mice
Lei, C., Liu, C., Peng, Y., Zhan, Y., Zhang, X., Liu, T., & Liu, Z. (2023) · iMeta · doi:10.1002/imt2.97 · Cited by 15 · see citing works
“Moreover, Jiang et al. [16] found that butyrate supplementation elevated the levels of synapse ‐ associated proteins and behavioral performance in mice with AD.”
BackgroundLi, Y., Wang, Z., Li, J., Yu, Y., Wang, Y., Jin, X., Dong, Y., Liu, Q., Duan, X., & Yan, N. (2023) · Biological Trace Element Research · doi:10.1007/s12011-023-03583-6 · Cited by 15 · see citing works
Inherent potential of mitochondria-targeted interventions for chronic neurodegenerative diseases
Zhou, M., Zheng, M., Liang, S., Li, M., Ma, J., Zhang, S., Song, X., Hu, Y., Lyu, Y., Ou, X., et al. (2025) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-01507 · Cited by 14 · see citing works
The role of gut microbiota in diabetic peripheral neuropathy rats with cognitive dysfunction
Huang, W., Lin, Z., Sun, A., Deng, J.-M., Manyande, A., Xiang, H., Zhao, G. F., & Hong, Q. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1156591 · Cited by 14 · see citing works
“In our experiments, we determined that Ruminococcaceae, a member of Firmicutes, was also less abundant in CD group than in NCD group; both Ruminococcaceae and Clostridium are gut microbiota that are beneficial for cognitive function; Ruminococcaceae produces butyrate, inhibits histone deacetylase, attenuates the secre…”
MethodZhang, Y., Huang, H. M., Yao, C., Sun, X., He, Q., Choudharyc, M. I., Chen, S., Liu, X., & Jiang, N. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1173920 · Cited by 14 · see citing works
“Research has found that SYP decreased and pro-inflammatory factors increased in mice with Alzheimer’s disease, and increasing the expression of SYP can ameliorate the impairment of the synaptic transmission effect in cognitive impairment (Liu et al., 2020; Jiang et al., 2021).”
BackgroundCorrelation between APOE4 gene and gut microbiota in Alzheimer’s disease
Chen, X.-X., Zeng, M.-X., Cai, D., Zhou, H.-H., Wang, Y., & Liu, Z. (2023) · Beneficial Microbes · doi:10.1163/18762891-20220116 · Cited by 14 · see citing works
Frataxin deficiency shifts metabolism to promote reactive microglia via glucose catabolism
Sciarretta, F., Zaccaria, F., Ninni, A., Ceci, V., Turchi, R., Apolloni, S., Milani, M., Valle, I. D., Tiberi, M., Chiurchiù, V., et al. (2024) · Life Science Alliance · doi:10.26508/lsa.202402609 · Cited by 13 · see citing works
“Dietary butyrate ameliorates microglia-mediated neuroin fl ammation in several in fl ammatory mouse models (Jiang et al, 2021; Wei et al, 2023) and improves cognitive decline following neuroin fl ammatory neurotoxin injection (Ge et al, 2023).”
Altered cognitive function in obese patients: relationship to gut flora
Deng, M., Tang, F., & Zhu, Z. (2025) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-024-05201-y · Cited by 12 · see citing works
“Ruminococcus spp. produce butyrate, which inhibits histone deacetylase, reduces the secretion of pro-inflammatory cytokines, and improves cognitive functions [70].”
Saadh, M. J., Ahmed, H. H., Kareem, R. A., Sanghvi, G. V., Ganesan, S., Agarwal, M., Kaur, P., Taher, W. M., Alwan, M., Jawad, M. J., et al. (2025) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2025.173972 · Cited by 12 · see citing works
Dong, J., Xie, T., Shi, C., Feng, G., Zhang, H., Xu, Z., & Dong, L. (2025) · Journal of Inflammation Research · doi:10.2147/jir.s543912 · Cited by 12 · see citing works
“130 Other HDAC inhibitors such as valproic acid have shown similar anti-inflammatory effects, acting through the STAT3/NF-κB axis to suppress microglia-mediated neuroinflammation in SCI models.”
Zhang, Q., Li, H., Yin, S., Feng, X., Chen, G., Zhou, J., Liu, K., & Cheng, Y. (2024) · Translational Pediatrics · doi:10.21037/tp-24-128 · Cited by 11 · see citing works
Ameen, A. O., Nielsen, S. W., Kjær, M. W., Andersen, J. V., Westi, E., Freude, K., & Aldana, B. (2024) · Journal of Cerebral Blood Flow and Metabolism · doi:10.1177/0271678x241270457 · Cited by 11 · see citing works
“16,17 Studies in Alzheimer’s disease (AD), wild-type (WT) and germ free (GF) mice have further demonstrated the transmission of AD pathogenesis and cognitive decline via microbiota.”
Ricciardi, N. R., Modarresi, F., Lohse, I., Andrade, N. S., Newman, I. A., Brown, J. M., Borja, C., Marples, B., Wahlestedt, C., & Volmar, C. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03373-0 · Cited by 11 · see citing works
Nohesara, S., Abdolmaleky, H. M., Thiagalingam, S., & Zhou, J. (2023) · Epigenomics · doi:10.2217/epi-2023-0342 · Cited by 17 · see citing works
Wen, J., Xu, Q., Li, J., Shen, X., Zhou, X., Huang, J., & Liu, S. (2024) · Scientific Reports · doi:10.1038/s41598-024-55198-z · Cited by 10 · see citing works
Zhang, C., Tan, R., Zhou, X., Wang, R., Wang, X., Ma, R., Chu, F., Li, Y., Yin, T., & Liu, Z. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25094651 · Cited by 9 · see citing works
“The long-term potentiation (LTP) and long-term depotentiation (DEP) protocols were similar to those in prior studies [85,86].”
ResultFasina, O. B., Li, L., Chen, D., Yi, M., Xiang, L., & Qi, J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252111719 · Cited by 9 · see citing works
From Obesity to Mitochondrial Dysfunction in Peripheral Tissues and in the Central Nervous System
Marino, F., Petrella, L., Cimmino, F., Pizzella, A., Monda, A., Allocca, S., Rotondo, R., D’Angelo, M., Musco, N., Iommelli, P., et al. (2025) · Biomolecules · doi:10.3390/biom15050638 · Cited by 10 · see citing works
“Thus, it may be involved in regulating neural plasticity and preventing the development of NDDs [200,201].”
Therapeutic Potential of Sodium Butyrate in Neurological and Psychiatric Disorders
Rahmani, D., Chodari, L., Kakallahpour, M., & Niknam, Z. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05428-w · Cited by 9 · see citing works
“Sodium butyrate (NaB), which is a member of the SCFAs family and the sodium form of the endogenous butyrate generated by gut microbiota, is a type of HDACI with the ability to decrease pro-inflammatory cytokines [21, 28, 29].”
The complement cascade in Alzheimer’s disease: modern implications of an ancient immune protagonist
Papavergi, M.-T., Bathini, P., Singh, B. B., & Lemere, C. A. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00916-y · Cited by 10 · see citing works
“It has been shown that early intervention with sodium butyrate in 5xFAD mice inhibits Aβ deposition [401, 402].”
Activation of β2-adrenergic receptors prevents AD-type synaptotoxicity via epigenetic mechanisms
Jin, M., Wei, Z., Ramalingam, N., Xiao, M., Xu, A., Yu, X., Song, Q., Liu, W., Zhao, J., Zhang, D., et al. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02145-5 · Cited by 8 · see citing works
Shi, W., Wu, X., Yuan, C., Kuang, T., Xie, X., Gong, W., Li, F., Shen, L., Zhang, Y., & Liang, X. (2024) · European journal of medical research · doi:10.1186/s40001-024-02142-6 · Cited by 8 · see citing works
“The MWM test is a classical method that can be adopted for evaluating spatial learning and long-term memory, and the specific process has been previously described [18].”
Natural products: Harnessing the power of gut microbiota for neurological health
Cheng, H., Liu, J., Zhang, D., Wu, J., Wu, J., Zhou, Y., Tan, Y., Feng, W., & Peng, C. Y. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.156019 · Cited by 7 · see citing works
Dissecting the immune response of CD4+ T cells in Alzheimer’s disease
Kostić, M. S., Živković, N., Cvetanović, A., Bašić, J., & Stojanović, I. R. (2024) · Reviews in the Neurosciences · doi:10.1515/revneuro-2024-0090 · Cited by 8 · see citing works
Bellitto, D., Bozzo, M., Ravera, S., Bertola, N., Rosamilia, F., Milia, J., Barboro, P., Vargas, G. C., Lisa, D. D., Pastorino, L., et al. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103544 · Cited by 6 · see citing works
“Nevertheless, several studies reported the involvement of butyrate, a short-chain fatty acid from which butanoate is derived, in reducing pro-inflammatory cytokines and improving synaptic plasticity in animal models of AD and PD [99 – 101].”
Does the Maternal Gut Microbiome Influence the Outcome of Perinatal Asphyxia?
Morozan, V.-P., Ionescu, M.-I., Zahiu, C. D. M., Catrina, A. M., Racoviță, A., Chirilă, A.-T., Dogaru, I.-A., Ciotei, C., Pîrcălăbioru, G. G., & Zăgrean, A. (2025) · Antioxidants · doi:10.3390/antiox14091134 · Cited by 7 · see citing works
“…animal models (induced through high-fat diet), butyrate improves mitochondrial function in the cerebral cortex and the synaptic fraction [192], enhances neuroplasticity [193], and shows an impressive neuroprotective effect in ischemia [142,194], all increasing the neural functional reserve.”
- Authors
- Jiang, Y., Li, K., Li, X., Xu, L., & Yang, Z.
- Affiliations
- Nankai University (CN)
- Corresponding author
- Yang, Zhuo
- Venue
- Chemico-Biological Interactions
- Publisher
- Elsevier BV
- Published
- 2021-05
- Volume
- 341
- Pages
- 109452
- ISSN
- 0009-2797 (ISSN-L)
- OpenAlex
- W3146836254
- Cited by
- 154
- References
- 54
- Citations by year
- 2026: 24 · 2025: 33 · 2024: 29 · 2023: 39 · 2022: 23 · 2021: 6
- FWCI
- 15.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Chemico-Biological Interactions (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- sodium butyrate, Alzheimer's disease, synaptic plasticity, neuroinflammation, microglial activation, amyloid-beta, 5xFAD mice, histone deacetylase inhibition, short-chain fatty acids, inflammatory cytokines, long-term potentiation, dendritic spines, synaptic proteins, early Alzheimer's disease
- MeSH terms
- Disks Large Homolog 4 Protein, Morris Water Maze Test, Alzheimer Disease, Animals, Brain, Disease Models, Animal, Inflammation, Mice, Transgenic, Neuronal Plasticity, Amyloid beta-Peptides, Synaptophysin, Microglia, Long-Term Potentiation, Butyric Acid, Cognitive Dysfunction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
