20- Deoxyingenol attenuate morphine-induced hippocampus neurotoxicity and memory impairments in rats
Jianfeng Ma,
Linfang Zou,
Yani Lou,
Yuanqu Lin,
Jiansong Zhou,
Nanbin Ju,
Jun Pan,
Xutong Zhang,
Dansi Qi
Affiliations
Jianfeng Ma
Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, China; Corresponding author. Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Linfang Zou
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China
Yani Lou
Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, China
Yuanqu Lin
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China
Jiansong Zhou
Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, China
Nanbin Ju
Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, China
Jun Pan
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China; Corresponding authors.
Xutong Zhang
Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, China; Corresponding author. Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Dansi Qi
Department of Pathology, Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China; Corresponding author.
Objective: The present study aimed to see if 20-Deoxyingenol(20-DOI) could protect hippocampus neurons from the neurotoxic effects of morphine and reduce memory loss in rats. Method: Male Wistar rats were given morphine hydrochloride (45 mg/kg, sc, four weeks) and 20-DOI (10, 20 mg/kg, ip., coadministered with morphine) for the Morris Water Maze (MWM) test to investigate the effects of 20-DOI on spatial learning and memory. Western blotting was used to evaluate the expression of the hippocampal CA1 region of the cleaved caspase-3, Bax, and Bcl2 proteins and so on. Moreover, these assays were used to evaluate the expression of superoxide dismutase (SOD)2, heme oxygenase 1(HO1) protein, and glutathione peroxidase (GPx) activity within the hippocampus CA1 area. Results: The administration of 20-DOI (10 and 20 mg/kg) to morphine-treated mice enhanced spatial learning and reduced memory deficits. Additionally, 20-DOI treatment reduced apoptosis and oxidative stress in the hippocampal CA1 region of morphine-treated rats. Moreover, 20-DOI improved the autophagy level of the hippocampal CA1 area of morphine-treated rats using Transcription factor EB (TFEB), and 20-DOI prevented spatial learning and memory impairment in morphine-treated rats. The current observation could be partially due to the inhibition of neuronal apoptosis and oxidative stress in the hippocampal CA1 region of rats treated with morphine and the improved autophagy in this region. Conclusions: 20-DOI attenuated morphine administration in rats with chronic disease caused spatial learning and memory dysfunction. These mechanistic effects could be partially related to 20-DOI protecting the CA1 region of rat hippocampal neurons from the morphine-induced oxidative stress, apoptosis, and autophagy through TFEB.
