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.

• Authors: Ali Nesari, Mohammad Taghi Mansouri, Mohammad Javad Khodayar, Mohsen Rezaei
• Journal: Nutritional neuroscience (Nutr Neurosci) Vol. 24 Issue 2 Pg. 119-129 (Feb 2021) ISSN: 1476-8305 [Electronic] England
• PMID: 31084475 (Publication Type: Journal Article)

Chemical References

• Neuroprotective Agents
• Proteasome Inhibitors
• Proteasome Endopeptidase Complex
• alpha-Tocopherol

Topics

• Animals
• Hippocampus (drug effects, metabolism)
• Male
• Memory, Long-Term (drug effects)
• Mitochondria (drug effects, metabolism)
• Neuroprotective Agents (administration & dosage)
• Oxidative Stress (drug effects)
• Proteasome Endopeptidase Complex
• Proteasome Inhibitors (administration & dosage)
• Rats, Wistar
• alpha-Tocopherol (administration & dosage)
• Rats