2. Academic Validation
  3. 3BDO Alleviates Seizures and Improves Cognitive Function by Regulating Autophagy in Pentylenetetrazol (PTZ)-Kindled Epileptic Mice Model

3BDO Alleviates Seizures and Improves Cognitive Function by Regulating Autophagy in Pentylenetetrazol (PTZ)-Kindled Epileptic Mice Model

  • Neurochem Res. 2022 Oct 15. doi: 10.1007/s11064-022-03778-8.
Meiwen Guo # 1 2,  Shuang Chen # 1 3,  Jitong Lao 1 4,  Jiantang Liang 1 2,  Hao Chen 1 2,  Jingyi Tong 1 2,  Yonghao Huang 5,  Dandan Jia 6 7,  Qifu Li 8 9
Affiliations

Affiliations

  • 1 Department of Neurology, the First Affiliated Hospital of Hainan Medical University, Haikou, China.
  • 2 Key Laboratory of Brain Science Research & Transformation in Tropical Environment of Hainan Province, Hainan Medical University, Haikou, China.
  • 3 Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 4 The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
  • 5 Hainan Medical University, Haikou, China.
  • 6 Department of Neurology, the First Affiliated Hospital of Hainan Medical University, Haikou, China. [email protected].
  • 7 Key Laboratory of Brain Science Research & Transformation in Tropical Environment of Hainan Province, Hainan Medical University, Haikou, China. [email protected].
  • 8 Department of Neurology, the First Affiliated Hospital of Hainan Medical University, Haikou, China. [email protected].
  • 9 Key Laboratory of Brain Science Research & Transformation in Tropical Environment of Hainan Province, Hainan Medical University, Haikou, China. [email protected].
  • # Contributed equally.
PMID: 36243819 DOI: 10.1007/s11064-022-03778-8
Abstract

3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3 H)-one (3BDO) is a mTOR agonist that inhibits Autophagy. The main purpose of this study is to investigate the effects of 3BDO on seizure and cognitive function by Autophagy regulation in pentylenetetrazol (PTZ)-kindled epileptic mice model. The PTZ-kindled epileptic mice model was used in study. The behavioral changes and electroencephalogram (EEG) of the mice in each group were observed. The cognitive functions were tested by Morris water maze test. The loss of hippocampal neurons was detected by hematoxylin-eosin (HE) staining and immunofluorescence analysis. Immunohistochemistry, western blot and q-PCR were employed to detect the expression of autophagy-related proteins and mTOR in the hippocampus and cortex. Less seizures, increased hippocampal neurons and reduced astrocytes of hippocampus were observed in the 3BDO-treated epileptic mice than in the PTZ-kindled epileptic mice. Morris water maze test results showed that 3BDO significantly improved the cognitive function of the PTZ-kindled epileptic mice. Western blot analyses and q-PCR revealed that 3BDO inhibited the expression of LC3, Beclin-1, Atg5, Atg7 and p-ULK1/ULK1, but increased that of p-mTOR/mTOR, p-P70S6K/P70S6K in the hippocampus and temporal lobe cortex of epileptic mice. Immunohistochemistry and immunofluorescence also showed 3BDO inhibited the LC3 expression and increased the mTOR expression in the hippocampus of epileptic mice. In addition, the Autophagy activator EN6 reversed the decrease in the 3BDO-induced Autophagy and aggravated the seizures and cognitive dysfunction in the epileptic mice. 3BDO regulates Autophagy by activating the mTOR signaling pathway in PTZ-kindled epileptic mice model, thereby alleviating hippocampus neuronal loss and astrocytes proliferation, reducing seizures and effectively improving cognitive function. Therefore, 3BDO may have potential value in the treatment of epilepsy.

Keywords

3BDO; Epilepsy; Epileptic model; PTZ; mTOR.

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