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

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.

KEYWORDS:

• Rat
• Proteasome
• Mitochondria
• Alpha-tocopherol
• Memory
• Reactive Oxygen Species

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes on contributors

Ali Nesari obtained his M.Sc. degree in toxicology from the Jundishapur University of Medical Sciences, Ahvaz, Iran. He has been working as a research assistant in the Jundishapur University of Medical Sciences since 2016 and his current research focuses on toxicological neuroscience.

Mohammad Taghi Mansouri is a research assistant professor at Columbia University, New York. He received his doctorate of pharmacology from Mashhad University of Medical Sciences, Mashhad, Iran. His current field of research focused on neuroscience and behavioral pharmacology.

Mohammad Javad Khodayar is an associate professor of toxicology at the Jundishapur University of Medical Sciences, Ahvaz, Iran. He obtained his doctorate in behavioral toxicology from Shahid Beheshti University of Medical Sciences, Tehran, Iran. His research interests include neuroscience and behavioral toxicology.

Mohsen Rezaei is an assistant professor of toxicology at the University of Tarbiat Modares, Tehran, Iran. He received his doctorate in molecular toxicology from Shahid Beheshti University of Medical sciences, Tehran, Iran. He has coauthored many publications in the field of cancer, diabetes and neurodegeneratives with focusing on the mitochondria. His research interests include mitochondria-associated pathogenesis and treatment of diabetes, cancer and neurodegenerative disorders.

Additional information

Funding

This work was supported by the Ahvaz Jundishapur University of Medical Sciences [grant number TRC_ 9310].