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Preadministration of high-dose alpha-tocopherol improved memory impairment and mitochondrial dysfunction induced by proteasome inhibition in rat hippocampus.

Authors
  • Nesari, Ali1
  • Mansouri, Mohammad Taghi2, 3
  • Khodayar, Mohammad Javad1, 4
  • Rezaei, Mohsen4, 5
  • 1 Department of Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. , (Iran)
  • 2 Department of Pharmacology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. , (Iran)
  • 3 Department of Anesthesiology, Irving Medical Center, Columbia University, New York, NY, USA.
  • 4 Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. , (Iran)
  • 5 Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. , (Iran)
Type
Published Article
Journal
Nutritional Neuroscience
Publisher
Maney Publishing
Publication Date
Feb 01, 2021
Volume
24
Issue
2
Pages
119–129
Identifiers
DOI: 10.1080/1028415X.2019.1601888
PMID: 31084475
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Objective: The ubiquitin-proteasome system plays a key role in memory consolidation. Proteasome inhibition and free radical-induced neural damage were implicated in neurodegenerative states. In this study, it was tested whether alpha-tocopherol (αT) in low and high doses could improve the long-term memory impairment induced by proteasome inhibition and protects against hippocampal oxidative stress. Methods: Alpha-tocopherol (αT) (60, 200 mg/kg, i.p. for 5 days) was administered to rats with memory deficit and hippocampal oxidative stress induced by bilateral intra-hippocampal injection of lactacystin (32 ng/μl) and mitochondrial evaluations were performed for improvement assessments. Results: The results showed that lactacystin significantly reduced the passive avoidance memory performance and increased the level of malondialdehyde (MDA), reactive oxygen species (ROS) and diminished the mitochondrial membrane potential (MMP) in the rat hippocampus. Furthermore, Intraperitoneal administration of αT significantly increased the passive avoidance memory, glutathione content and reduced ROS, MDA levels and impaired MMP. Conclusions: The results suggested that αT has neuroprotective effects against lactacystin-induced oxidative stress and memory impairment via the enhancement of hippocampal antioxidant capacity and concomitant mitochondrial sustainability. This finding shows a way to prevent and also to treat neurodegenerative diseases associated with mitochondrial impairment.

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