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Sevoflurane exposure during the second trimester induces neurotoxicity in offspring rats by hyperactivation of PARP-1.

Rationale: Fetal exposure to general anesthesia may cause noteworthy neurocognitive impairment, but the mechanisms are unclear. Objectives: Our study designed to explore the potential mechanism of neurotoxicity in offspring rats after sevoflurane exposure to the pregnant rats during the second trime...

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Published in:Psychopharmacology Vol. 239; no. 9; pp. 3031 - 3046
Main Authors: Wang, Cong, Jiang, Qian, Zhao, Ping
Format: Journal Article
Published: Springer Nature Sep2022
Online Access:View this record in EBSCOhost
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      dt: Sep2022
      vid: 239
      iid: 9
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      pub: Springer Nature
      place: New York, New York
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        158077570
        10.1007/s00213-022-06188-4
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        atl: Sevoflurane exposure during the second trimester induces neurotoxicity in offspring rats by hyperactivation of PARP-1.
      aug:
        au:
          Wang, Cong
          Jiang, Qian
          Zhao, Ping
        affil: Department of Anesthesiology, Shengjing Hospital of China Medical University, No 36 Sanhao Street, Heping District Liaoning Province, 110004, Shenyang, China
      sug:
      ab: Rationale: Fetal exposure to general anesthesia may cause noteworthy neurocognitive impairment, but the mechanisms are unclear. Objectives: Our study designed to explore the potential mechanism of neurotoxicity in offspring rats after sevoflurane exposure to the pregnant rats during the second trimester. Methods: Pregnant rats (G14 day) were administrated with or without 3.5% sevoflurane, 40 mg/kg 3-aminobenzamide (3-AB), inhibitor of poly ADP ribose polymerase 1 (PARP-1), or 10 mg/kg TC-2153, inhibitor of striatal-enriched phosphatase 61 (STEP61). Afterwards, the effects on expression of β-tubulin (TUJ1), neurite outgrowth inhibitor A (Nogo-A), parthanatos-related and STEP61/proline-rich tyrosine kinase 2 (Pyk2) pathway-associated proteins, and reactive oxygen species (ROS) levels were examined by immunofluorescence staining, Western blot, and dihydroethidium (DHE) staining, respectively. Moreover, morphological changes in the hippocampal CA3 region and neuronal cell death were tested by glycine silver staining and TUNEL and immunofluorescence double staining, respectively. Furthermore, spatial learning and memory functions of rats on postnatal 28–33 days (PND 28–33) were evaluated by morris water maze (MWM). Results: Mid-pregnancy exposure to sevoflurane led to excessive PARP-1 activation, poly (ADP-ribose) (PAR) polymer accumulation, apoptosis-inducing factor (AIF) nuclear translocation, and Nogo-A accumulation. Besides, sevoflurane significantly inhibited neurite growth and increased cell death in the fetal rat brain. Additionally, sevoflurane activated STEP61/Pyk2 pathway and increased ROS levels. However, 3-AB or TC-2153 significantly alleviated cell death, promoted neurites growth, and improved sevoflurane-induced spatial learning and memory impairment. Conclusion: This study proposes that sevoflurane exposure during the second trimester incudes neurotoxicity in offspring rats by hyperactivation of PARP-1 via STEP61/Pyk2 pathway.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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