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YUE Ling-feng, ZHONG Zhao-xi, MA Jing, et al. The Protective Effect of Olanzapine on the Hippocampal Neuron of Depression Model Rats via Inhibiting NLRP3 Inflammasome Activation[J]. Journal of Sichuan University (Medical Sciences), 2019, 50(5): 672-678.
Citation: YUE Ling-feng, ZHONG Zhao-xi, MA Jing, et al. The Protective Effect of Olanzapine on the Hippocampal Neuron of Depression Model Rats via Inhibiting NLRP3 Inflammasome Activation[J]. Journal of Sichuan University (Medical Sciences), 2019, 50(5): 672-678.

The Protective Effect of Olanzapine on the Hippocampal Neuron of Depression Model Rats via Inhibiting NLRP3 Inflammasome Activation

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  • Corresponding author:

    ZHONG Zhao-xi . E-mail:zzxzzx9268@tom.com

  • Received Date: February 18, 2019
  • Revised Date: May 28, 2019
  • Available Online: March 16, 2021
  • Published Date: September 19, 2019
  •   Objective  To determine the impact olanzapine (OLA) on the hippocampal neuron of model rats with depression.
      Methods  Rats were divided into five groups: control, chronic unpredicted stress (CUS), OAL (0.5, 1, 2 mg/kg), si-Atg5, and OAL (2 mg/kg)+si-Atg5. Open field and sucrose preference tests were performed to evaluate rat behaviors. Cell apoptosis was detected with Tunnel. The concentrations of interleukin (IL)-1β and IL-18 were determined by ELISA. The expressions of cleaved Caspase-3, cleaved Caspase-9, LC3, Beclin1, P62, NLRP3 and cleaved Caspase-1 were measured by Western blot.
      Results  OAL (0.5, 1, 2 mg/kg) increased the total moving distance, sucrose consumption and preference rate of CUS rats, and decreased serum IL-18, cell apoptosis and the expressions of cleaved Caspase-9, cleaved Caspase-1 and NLRP3 in the CA3 region of hippocampus. Although OAL (1, 2 mg/kg) decreased the expression of cleaved Caspase-3 and serum IL-1β, OAL (0.5 mg/kg) showed no detectable effects. Si-Atg5 decreased the total moving distance, sucrose consumption and preference rate of CUS rats, enhanced the expressions of cleaved Caspase-3, cleaved Caspase-9, cleaved Caspase-1 and NLRP3, and weakened the effect of OAL (2 mg/kg). OAL (0.5, 1, 2 mg/kg) also increased the LC3Ⅱ/LC3Ⅰ ratio and the expression of Beclin1 in the CA3 region of hippocampus. OAL (1, 2 mg/kg) reduced the expression of p62, but not when it was reduced to 0.5 mg/kg. Si-Atg5 reduced the LC3Ⅱ/LC3Ⅰ ratio and the expression of Beclin1, and weakened the function of OAL (2 mg/kg).
      Conclusion  OAL can protect the hippocampal neuron of CUS rats via inhibiting NLRP3 inflammasome activation.
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