Open Access

CB2R orchestrates neuronal autophagy through regulation of the mTOR signaling pathway in the hippocampus of developing rats with status epilepticus

  • Authors:
    • Qiong Wu
    • Miao Zhang
    • Xueyan Liu
    • Junmei Zhang
    • Hua Wang
  • View Affiliations

  • Published online on: December 23, 2019     https://doi.org/10.3892/ijmm.2019.4439
  • Pages: 475-484
  • Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Neuronal loss and gliosis are the major pathological changes after status epilepticus (SE). The authors' previous study revealed the time‑dependent changes of cannabinoid receptor type 2 (CB2R) in hippocampal neurons of developing rats after SE, which were accompanied by a decrease in the number of neurons. Meanwhile, growing evidence indicates that CB2R stimulation exerts anti‑convulsant properties in seizure models. However, the activation of CB2R in neuronal repair in response to the damage after SE is still unclear. In this experiment, a highly‑selective CB2R agonist JWH133 and antagonist AM630 were administered to determine the activity of CB2R in neuronal autophagy and apoptosis of the post‑SE repair in developing rats. The present results revealed that activation of CB2R by JWH133, not only obviously lowered the success rate, 24‑h death rate and the Racine stage in the model, but also extended the latency period to SE. In addition, compared with the vehicle control group, CB2R activation increased neuronal autophagy and the expression of phosphorylated‑mammalian target of rapamycin (p‑mTOR)/mTOR, Beclin‑1, and LC3II/LC3I while decreasing the expression of p‑Unc‑51‑like autophagy‑activating kinase 1 (ULK‑1)/ULK1, p62, and cleaved caspase‑3. These results were dose‑dependent and were especially evident in the high‑dose group, and interestingly the opposite results were obtained in the AM630 group. Thus, CB2R orchestrates neuronal autophagy through regulation of the mTOR signaling pathway in the hippocampus of developing rats with SE. These findings might provide an important basis for further investigation of the therapeutic role of CB2R in ameliorating epilepsy‑related neuronal damage.
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February 2020
Volume 45 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Wu, Q., Zhang, M., Liu, X., Zhang, J., & Wang, H. (2020). CB2R orchestrates neuronal autophagy through regulation of the mTOR signaling pathway in the hippocampus of developing rats with status epilepticus. International Journal of Molecular Medicine, 45, 475-484. https://doi.org/10.3892/ijmm.2019.4439
MLA
Wu, Q., Zhang, M., Liu, X., Zhang, J., Wang, H."CB2R orchestrates neuronal autophagy through regulation of the mTOR signaling pathway in the hippocampus of developing rats with status epilepticus". International Journal of Molecular Medicine 45.2 (2020): 475-484.
Chicago
Wu, Q., Zhang, M., Liu, X., Zhang, J., Wang, H."CB2R orchestrates neuronal autophagy through regulation of the mTOR signaling pathway in the hippocampus of developing rats with status epilepticus". International Journal of Molecular Medicine 45, no. 2 (2020): 475-484. https://doi.org/10.3892/ijmm.2019.4439