Sodium butyrate improves memory function in an Alzheimer's disease mouse model when administered at an advanced stage of disease progression
Open accessAbstract
Dysregulation of histone acetylation has been implicated in the onset of age-associated memory impairment and the pathogenesis of neurodegenerative diseases. Elevation of histone acetylation via administration of histone deacetylase (HDAC) inhibitors is currently being pursued as a novel therapeutic avenue to treat memory impairment linked to Alzheimer's disease (AD). Here we show that severe amyloid pathology correlates with a pronounced dysregulation of histone acetylation in the forebrain of APPPS1-21 mice. Importantly, prolonged treatment with the pan-HDAC inhibitor sodium butyrate improved associative memory in APPPS1-21 mice even when administered at a very advanced stage of pathology. The recovery of memory function correlated with elevated hippocampal histone acetylation and increased expression of genes implicated in associative learning. These data advance our understanding of the potential applicability of HDAC inhibitors for the treatment of AD and suggest that HDAC inhibitors may have beneficial effects even when administered long after the onset of disease-associated symptoms.
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Key neuropathological processes underlying AD might also be modulated by SCFAs.
“Accumulating evidence has demonstrated that key neuropathological processes underlying AD might also be modulated by SCFAs (25, 34, 158, 159).”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [158]
Through HDAC inhibition, butyrate administration recovered memory function and increased expression of genes implicated in associative learning in the APP/PS1 mouse model of AD.
“Finally, through HDAC inhibition, butyrate administration recovered memory function and increased expression of genes implicated in associative learning in the APP/PS1 mouse model of AD (158).”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [158]
The indexed copy provides a repository listing for the paper (Journal of Alzheimer’s Disease 26(1), pp. 187–197), but the passages returned for associative-learning genes and HDAC inhibition are from its abstract, not its full text. Searches for those terms returned no results or discussion passage from the paper, so the attributed findings cannot be verified from the available eligible text. (LLM, conf=0.72)
Experimental — accuracy not yet measuredBenzamide compound 1 has a significantly different binding mode, in which the thiophene group is inserted into the foot pocket.
“The benzamide compound 1 has a significantly different binding mode, in which the thiophene group is inserted into the 'foot pocket' (Fig. 3 B ) (20-23, 32, 33).”
From Histone Deacetylase (HDAC) Inhibitor Kinetic Rate Constants Correlate with Cellular Histone Acetylation but Not Transcription and Cell Viability (2013) · cites this paper as [21]
The available indexed text under the Journal of Alzheimer's Disease 26(1), pp. 187–197 listing discusses sodium butyrate, histone acetylation, and memory in an Alzheimer’s mouse model. Searches for “benzamide compound 1,” “thiophene,” and “foot pocket” found no passage addressing the claimed binding mode. The available copy therefore does not verify this attribution. (LLM, conf=0.78)
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- Authors
- Govindarajan, N., Agis-Balboa, R. C., Walter, J., Sananbenesi, F., & Fischer, A.
- Affiliations
- Universitätsmedizin Göttingen (DE)
- Laboratory of Aging and Cognitive Diseases, European Neuroscience Institute Goettingen, University Medicine Goettingen, Goettingen, Germany
- Corresponding author
- Fischer, André
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2011-08-26
- Volume
- 26
- Issue
- 1
- Pages
- 187-197
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1883566698
- Cited by
- 405
- References
- 3
- Citations by year
- 2026: 26 · 2025: 31 · 2024: 45 · 2023: 45 · 2022: 41 · 2021: 38 · 2020: 27 · 2019: 17 · 2018: 22 · 2017: 20 · 2016: 16 · 2015: 12 · 2014: 21 · 2013: 24 · 2012: 16
- FWCI
- 13.97
- Type
- journal article
- Language
- en
- Open access
- green
- orbilu.uni.lu
- Licence
- cc-by-nc-sa
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Open Repository and Bibliography (University of Luxembourg) (submittedVersion, cc-by-nc-sa)
- GRO (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Hans und Ilse Breuer-Stiftung
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- sodium butyrate, Alzheimer's disease
- MeSH terms
- Acetylation, Alzheimer Disease, Analysis of Variance, Animals, Avoidance Learning, Brain, Butyrates, Disease Models, Animal, Electroshock, Exploratory Behavior, Gene Expression Regulation, Histones, Locomotion, Memory Disorders, Mice, Transgenic, Nerve Tissue Proteins, Amyloid beta-Protein Precursor, Microscopy, Confocal, Freezing Reaction, Cataleptic, Mice, Histone Acetyltransferases, Presenilin-1
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