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Sodium butyrate ameliorates the cognitive impairment of Alzheimer’s disease by regulating the metabolism of astrocytes

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Abstract

Rationale

Energy metabolism disorder is a widespread feature that exists in the early clinical stages of Alzheimer’s disease (AD). Astrocyte is the most numerous and the largest glial cell in the brain. By transporting energetic fuels such as lactate and ketones to neurons, astrocytes play a pivotal role in maintaining the cerebral energy homeostasis. Sodium butyrate (NaB), a type of short-chain fatty acid; its anti-inflammatory effect; and inhibition on histone deacetylases have been widely studied.

Methods

Spatial memory and cognitive ability of mice were assessed by using behavioral tests. Western blotting and ELISA kits were used to detect related protein levels and other biochemical markers, respectively.

Objectives

To prove the therapeutic effect of NaB on AD cognitive impairment and provide possible research ideas for mechanism exploration.

Results

Administration of NaB could improve the cognitive impairments induced by Aβ25–35 in mice. Furthermore, NaB could promote the differentiation of astrocytes towards A2-neuron-protective subtype, astroglial mitochondrial function, and lactate shuttle between astrocytes and neurons.

Conclusion

These findings reveal the effect of sodium butyrate on astrocytes, which may improve the pathological status of AD and provide experimental basis for sodium butyrate treatment of AD.

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Abbreviations

AD:

Alzheimer’s disease

NaB:

Sodium butyrate

GLUT2:

Glucose transporter protein 2

gWat:

Gonadal white adipose tissue

BBB:

Blood-brain barrier

PGC-1α:

Transcriptional coactivator for steroid receptors and nuclear receptors

MCT:

Monocarboxylate transporter

GFAP:

Glial fibrillary acidic protein

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Funding

This work was supported by the National Natural Science Foundation of China (No. 81673434) and “Double First-Class” University project (No. CPU2018GY22).

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Author notes

  1. Chen Wang and Dongpeng Zheng contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology, China Pharmaceutical University, No. 24 Tong Jia Xiang, Nanjing, 210009, Jiangsu Province, China

    Chen Wang, Dongpeng Zheng, Fanglin Weng, Yongzeng Jin & Ling He

Authors
  1. Chen Wang
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  2. Dongpeng Zheng
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  3. Fanglin Weng
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  4. Yongzeng Jin
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  5. Ling He
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Contributions

Ling He and Chen Wang designed this study and wrote the manuscript. Chen Wang, Dongpeng Zheng, and Fanglin Weng performed the experiments. Dongpeng Zheng and Fanglin Weng helped in collecting and analyzing the data. All authors listed have made direct contribution to this work, and approved it for publication.

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Correspondence to Ling He.

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Wang, C., Zheng, D., Weng, F. et al. Sodium butyrate ameliorates the cognitive impairment of Alzheimer’s disease by regulating the metabolism of astrocytes. Psychopharmacology 239, 215–227 (2022). https://doi.org/10.1007/s00213-021-06025-0

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  • DOI: https://doi.org/10.1007/s00213-021-06025-0

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