Histone Deacetylases May Mediate Surgery-Induced Impairment of Learning, Memory, and Dendritic Development

Abstract

Postoperative cognitive dysfunction (POCD) affects millions of patients each year in the USA and has been recognized as a significant complication after surgery. Epigenetic regulation of learning and memory has been shown. For example, an increase of histone deacetylases (HDACs), especially HDAC2, which epigenetically regulates gene expression, impairs learning and memory. However, the epigenetic contribution to the development of POCD is not known. Also, the effects of living situation on POCD have not been investigated. Here, we showed that mice that lived alone before the surgery and lived in a group after the surgery and mice that lived in a group before surgery and lived alone after surgery had impairment of learning and memory compared with the corresponding control mice without surgery. Surgery increased the activity of HDACs including HDAC2 but not HDAC1 and decreased brain-derived neurotrophic factor (BDNF), dendritic arborization, and spine density in the hippocampus. Suberanilohydroxamic acid (SAHA), a relatively specific inhibitor of HDAC2, attenuated these surgery effects. SAHA did not change BDNF expression, dendritic arborization, and spine density in mice without surgery. Surgery also reduced the activity of nuclear histone acetyltransferases (HATs). This effect was not affected by SAHA. Our results suggest that surgery activates HDACs, which then reduces BDNF and dendritic arborization to develop POCD. Thus, epigenetic change contributes to the occurrence of POCD.

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Funding

This study was supported by grants (GM098308, HD089999, AG061047, NS099118, and AG056995 to Z Zuo) from the National Institutes of Health, Bethesda, MD, and the Robert M. Epstein Professorship endowment, University of Virginia, Charlottesville, VA.

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ZZ conceived the project. FL, JM, and ZZ designed the study. FL, JM, and JW performed the experiments. FL and JM did the initial data analysis and drafted the “Materials and Methods” section. ZZ performed the final data analysis and wrote the manuscript.

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Correspondence to Zhiyi Zuo.

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Luo, F., Min, J., Wu, J. et al. Histone Deacetylases May Mediate Surgery-Induced Impairment of Learning, Memory, and Dendritic Development. Mol Neurobiol (2020). https://doi.org/10.1007/s12035-020-01987-2

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Keywords

  • Dendritic arborization
  • Epigenetic regulation
  • Histone deacetylase
  • POCD