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Cannabinoid receptor 2 deficiency enhances isoflurane-induced spatial cognitive impairment in adult mice by affecting neuroinflammation, neurogenesis and neuroplasticity

  • Authors:
    • Chao Li
    • Jingpu Shi
    • Jiaguang Sun
    • Yuanyuan Shi
    • Huiqun Jia
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, Department of Anesthesiology, Xingtai People's Hospital, Xintai, Hebei 054001, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 908
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    Published online on: June 25, 2021
       https://doi.org/10.3892/etm.2021.10340
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Abstract

Isoflurane (Iso) is a commonly used inhalational anesthetic and is associated with the incidence of postoperative cognitive dysfunction (POCD). Cannabinoid receptor 2 (CB2R) was previously reported to have a promising neuroprotective function in cases of POCD, but the specific mechanisms have remained to be fully explored. The aim of the present study was to investigate the effect of CB2R deficiency on spatial cognitive performance in adult mice exposed to Iso. A total of 20 adult CB2R knockout (KO) and 20 wild-type (WT) mice were exposed to Iso (1.4% in oxygen for 4 h) or 100% oxygen. The Morris water maze (MWZ) test was performed 10 days after Iso exposure. Immunofluorescence staining and reverse transcription-quantitative PCR were performed to assess the expression of microglial marker ionized calcium-binding adaptor molecule-1 (Iba1) and the mRNA expression levels of microglial phenotype markers (M1: Interleukin-6, tumor necrosis factor-α, inducible nitric oxide synthase; M2: Chitinase-3 like protein) in the hippocampus. Changes in hippocampal neurogenesis and neuroplasticity were assessed by 5-bromodeoxyuridine (BrdU) immunostaining and Golgi staining. Compared with control mice, WT Iso-exposed mice had impaired spatial performance in the MWZ test. Furthermore, hippocampal Iba1 immunoreactivity and the number of microglial branches were notably increased in Iso-exposed WT mice. This was paralleled by significant upregulation of M1-associated markers and downregulation of M2-associated markers in the hippocampus. An obviously reduced number of BrdU+ neurons and decreased spine density were observed in WT Iso-exposed mice compared with control mice. Of note, CB2R deficiency exacerbated the spatial cognition impairment induced by Iso in the MWZ test. The alterations in the activation, morphology and M1 polarization of microglia, the number of BrdU+ neurons and spine density were more pronounced in CB2R-deficient Iso-exposed KO mice than in WT Iso-exposed mice. These results suggested that CB2R has a crucial role in Iso-induced cognitive impairment, which may be related to changes in hippocampal neuroinflammation, neurogenesis and neuroplasticity.
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Copy and paste a formatted citation
Spandidos Publications style
Li C, Shi J, Sun J, Shi Y and Jia H: Cannabinoid receptor 2 deficiency enhances isoflurane-induced spatial cognitive impairment in adult mice by affecting neuroinflammation, neurogenesis and neuroplasticity. Exp Ther Med 22: 908, 2021.
APA
Li, C., Shi, J., Sun, J., Shi, Y., & Jia, H. (2021). Cannabinoid receptor 2 deficiency enhances isoflurane-induced spatial cognitive impairment in adult mice by affecting neuroinflammation, neurogenesis and neuroplasticity. Experimental and Therapeutic Medicine, 22, 908. https://doi.org/10.3892/etm.2021.10340
MLA
Li, C., Shi, J., Sun, J., Shi, Y., Jia, H."Cannabinoid receptor 2 deficiency enhances isoflurane-induced spatial cognitive impairment in adult mice by affecting neuroinflammation, neurogenesis and neuroplasticity". Experimental and Therapeutic Medicine 22.2 (2021): 908.
Chicago
Li, C., Shi, J., Sun, J., Shi, Y., Jia, H."Cannabinoid receptor 2 deficiency enhances isoflurane-induced spatial cognitive impairment in adult mice by affecting neuroinflammation, neurogenesis and neuroplasticity". Experimental and Therapeutic Medicine 22, no. 2 (2021): 908. https://doi.org/10.3892/etm.2021.10340
Copy and paste a formatted citation
x
Spandidos Publications style
Li C, Shi J, Sun J, Shi Y and Jia H: Cannabinoid receptor 2 deficiency enhances isoflurane-induced spatial cognitive impairment in adult mice by affecting neuroinflammation, neurogenesis and neuroplasticity. Exp Ther Med 22: 908, 2021.
APA
Li, C., Shi, J., Sun, J., Shi, Y., & Jia, H. (2021). Cannabinoid receptor 2 deficiency enhances isoflurane-induced spatial cognitive impairment in adult mice by affecting neuroinflammation, neurogenesis and neuroplasticity. Experimental and Therapeutic Medicine, 22, 908. https://doi.org/10.3892/etm.2021.10340
MLA
Li, C., Shi, J., Sun, J., Shi, Y., Jia, H."Cannabinoid receptor 2 deficiency enhances isoflurane-induced spatial cognitive impairment in adult mice by affecting neuroinflammation, neurogenesis and neuroplasticity". Experimental and Therapeutic Medicine 22.2 (2021): 908.
Chicago
Li, C., Shi, J., Sun, J., Shi, Y., Jia, H."Cannabinoid receptor 2 deficiency enhances isoflurane-induced spatial cognitive impairment in adult mice by affecting neuroinflammation, neurogenesis and neuroplasticity". Experimental and Therapeutic Medicine 22, no. 2 (2021): 908. https://doi.org/10.3892/etm.2021.10340
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