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Hippocampal Glutamate Level and Glutamate Aspartate Transporter (GLAST) are Up-Regulated in Senior Rat Associated with Isoflurane-Induced Spatial Learning/Memory Impairment

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Abstract

Postoperative cognitive decline is a clinical concern especially for senior patients. It is generally recognized that glutamatergic system plays a crucial role in the physiopathologic process of neurocognitive deterioration. However, alterations of glutamatergic system in prolonged isoflurane-induced learning/memory decline are still unclear. This study investigates the question whether glutamate concentration and corresponding transporters or receptors display any alternations in aged rat suffering from isoflurane-induced learning/memory impairment. 111 male Sprague–Dawley rats (>18 months) were randomly divided into two main groups: hippocampal microdialysis group (n = 38) and western blotting group (n = 73). Each group was subdivided into three subgroups including (1) control subgroup (n = 6 and 10, receiving no behavioral trial, anesthesia or air exposure); (2) air-exposed subgroup (n = 7 and 15, receiving behavioral trial and air exposure but not anesthesia); (3) isoflurane anesthesia subgroup (n = 25 and 48, receiving both behavioral trial and anesthesia). The isoflurane-exposed rats were further divided into a learning/memory-impaired subgroup and a non-learning/memory-impaired subgroup according to their behavioral performance, which was measured using Morris water maze. Hippocampal glutamate concentrations in microdialysates were determined by high-performance liquid chromatography. Expression levels of GLAST, GLT-1, NMDAR1, NMDAR2A/B, AMPAR and tau in hippocampus were assessed via quantitative Western blotting. The incidences of learning/memory impairment of isoflurane-exposed rats in hippocampal microdialysis group and western blotting group were 12.0 (3/25) and 10.4 % (5/48) respectively. The intra-anesthesia hippocampal glutamate levels were significantly lower than those of non-anesthesized rats. The learning/memory-impaired rats showed a long-lasting increased glutamate level from 24 h after isoflurane exposure to the end of the study, but the other 22 isoflurane-exposed rats did not. The learning/memory-impaired subgroup displayed a significantly higher GLAST level than the other three subgroups (p = 0.026, 0.02 and 0.032 respectively). The expression levels of GLT-1, NMDAR1, NMDAR2A/B and AMPAR of every subgroup were comparable. We found a continuous raised hippocampal glutamate and an up-regulation of GLAST rather than GLT-1, NMDAR1, NMDAR2A/B, AMPAR or tau in hippocampus of aged rats associated with isoflurane-induced learning/memory impairment.

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Acknowledgments

Our study was supported by National Natural Science Foundation of China (grant no. 30872425).

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Authors and Affiliations

  1. Beijing Chao-yang Hospital, Capital Medical University, Beijing, China

    Xiangdong Qu

  2. Anesthesia Department, Beijing Jishuitan Hospital, Beijing, China

    Xiangdong Qu

  3. Anesthesia Department, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China

    Chengshi Xu, Hui Wang, Jie Xu, Yun Wang, Anshi Wu & Yun Yue

  4. Department of Anesthesiology, Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China

    Weiran Liu

  5. Basic Medical Research Center, Capital Medical University Affiliated Beijing Chaoyang Hospital, Beijing, China

    Xingyuan Jia

  6. Geriatric Anesthesia Research Unit, Department of Anesthesia, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129-2060, USA

    Zhongcong Xie & Zhipeng Xu

  7. Department of Pharmacology, Institute of Basic Medical Sciences, School of Basic Medicine, PUMC & CAMS, Beijing, China

    Chao Ji

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  7. Xingyuan Jia
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  8. Zhongcong Xie
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  9. Zhipeng Xu
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  10. Chao Ji
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  11. Anshi Wu
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  12. Yun Yue
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Corresponding authors

Correspondence to Anshi Wu or Yun Yue.

Additional information

Xiangdong Qu and Chengshi Xu equal contribution to this study.

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Qu, X., Xu, C., Wang, H. et al. Hippocampal Glutamate Level and Glutamate Aspartate Transporter (GLAST) are Up-Regulated in Senior Rat Associated with Isoflurane-Induced Spatial Learning/Memory Impairment. Neurochem Res 38, 59–73 (2013). https://doi.org/10.1007/s11064-012-0889-8

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  • DOI: https://doi.org/10.1007/s11064-012-0889-8

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