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Enriched Environment Attenuates Surgery-Induced Impairment of Learning, Memory, and Neurogenesis Possibly by Preserving BDNF Expression

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Abstract

Postoperative cognitive dysfunction (POCD) is a significant clinical syndrome. Neurogenesis contributes to cognition. It is known that enriched environment (EE) enhances neurogenesis. We determined whether EE attenuated surgery-induced cognitive impairment and whether growth factors and neurogenesis played a role in the EE effect. Eight-week-old C57BL/6J mice were subjected to carotid artery exposure. Their learning and memory were assessed by Barnes maze, and fear conditioning started 2 weeks after the surgery. Growth factor expression and cell genesis were determined at various times after the surgery. Surgery increased the time for the mice to identify the target hole in the Barnes maze and reduced context-related freezing behavior. Surgery also reduced the expression of brain-derived neurotrophic factor (BDNF) and neurogenesis in the hippocampus. These effects were attenuated by EE. EE also attenuated surgery-induced reduction of phosphorylated/activated tropomyosin-related kinase B (TrkB) and extracellular signal-regulated kinases (ERK), components of BDNF signaling pathway. ANA-12, a selective TrkB antagonist, blocked the effects of EE on cognition, phosphorylation of TrkB and ERK, and neurogenesis. These results provide initial evidence that surgery reduces BDNF expression and neurogenesis in the hippocampus. Our results suggest that EE reduces surgery-induced impairment of learning, memory, and neurogenesis by preserving BDNF expression.

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Grant Support

This study was supported by grants (R01 GM065211 and R01 GM098308 to Z Zuo) from the National Institutes of Health, Bethesda, MD, by a grant from the International Anesthesia Research Society (2007 Frontiers in Anesthesia Research Award to Z Zuo), Cleveland, OH, by a grant from Commonwealth of Virginia Alzheimer’s and Related Disease Research Fund, Richmond, VA, by a Grant-in-Aid from the American Heart Association Mid-Atlantic Affiliate (10GRNT3900019 to Z Zuo), Baltimore, MD, and the Robert M. Epstein Professorship endowment, University of Virginia, Charlottesville, VA.

Author Contributions

Z.Z. conceived the concept of the project. D.F. and Z.Z. designed research; D.F., J.L., B.Z., and L.H. performed research; D.F., J.L., B.Z., and Z.Z. analyzed data; and D.F. and Z.Z. wrote the paper.

Conflicts of Interest

None.

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Authors and Affiliations

  1. Department of Anesthesiology, University of Virginia, Charlottesville, VA, 22908, USA

    Dan Fan, Jun Li, Bin Zheng, Lei Hua & Zhiyi Zuo

  2. Department of Anesthesiology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, 610072, China

    Dan Fan

  3. Department of Anesthesiology, Fourth Affiliated Hospital, Harbin Medical University, Harbin, 150001, China

    Jun Li

  4. Department of Anesthesiology, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, 510180, China

    Bin Zheng

  5. Department of Anesthesiology, Beijing Children’s Hospital, Beijing, 100045, China

    Lei Hua

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  1. Dan Fan
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  2. Jun Li
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  3. Bin Zheng
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  4. Lei Hua
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  5. Zhiyi Zuo
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Corresponding author

Correspondence to Zhiyi Zuo.

Additional information

The research work was performed in the Department of Anesthesiology, University of Virginia, Charlottesville, VA 22908, USA.

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Fan, D., Li, J., Zheng, B. et al. Enriched Environment Attenuates Surgery-Induced Impairment of Learning, Memory, and Neurogenesis Possibly by Preserving BDNF Expression. Mol Neurobiol 53, 344–354 (2016). https://doi.org/10.1007/s12035-014-9013-1

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  • DOI: https://doi.org/10.1007/s12035-014-9013-1

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