Rivastigmine Reverses the Decrease in Synapsin and Memory Caused by Homocysteine: Is There Relation to Inflammation?

Abstract

Elevated levels of homocysteine (Hcy) in the blood, called hyperhomocysteinemia (HHcy), is a prevalent risk factor for it has been shown that Hcy induces oxidative stress and increases microglial activation and neuroinflammation, as well as causes cognitive impairment, which have been linked to the neurodegenerative process. This study aimed to evaluate the effect of mild hyperhomocysteinemia with or without ibuprofen and rivastigmine treatments on the behavior and neurochemical parameters in male rats. The chronic mild HHcy model was chemically induced in Wistar rats by subcutaneous administration of Hcy (4055 mg/kg body weight) twice daily for 30 days. Ibuprofen (40 mg/kg) and rivastigmine (0.5 mg/kg) were administered intraperitoneally once daily. Motor damage (open field, balance beam, rotarod, and vertical pole test), cognitive deficits (Y-maze), neurochemical parameters (oxidative status/antioxidant enzymatic defenses, presynaptic protein synapsin 1, inflammatory profile parameters, calcium binding adapter molecule 1 (Iba1), iNOS gene expression), and cholinergic anti-inflammatory pathway were investigated. Results showed that mild HHcy caused cognitive deficits in working memory, and impaired motor coordination reduced the amount of synapsin 1 protein, altered the neuroinflammatory picture, and caused changes in the activity of catalase and acetylcholinesterase enzymes. Both rivastigmine and ibuprofen treatments were able to mitigate this damage caused by mild HHcy. Together, these neurochemical changes may be associated with the mechanisms by which Hcy has been linked to a risk factor for AD. Treatments with rivastigmine and ibuprofen can effectively reduce the damage caused by increased Hcy levels.

• Authors: Osmar Vieira Ramires Junior, Tiago Marcon Dos Santos, Josiane Silva Silveira, Raíssa Leite-Aguiar, Robson Coutinho-Silva, Luiz Eduardo Baggio Savio, Angela T S Wyse
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 59 Issue 7 Pg. 4517-4534 (Jul 2022) ISSN: 1559-1182 [Electronic] United States
• PMID: 35578101 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Synapsins
• Homocysteine
• Acetylcholinesterase
• Rivastigmine
• Ibuprofen

Topics

• Acetylcholinesterase (metabolism)
• Animals
• Homocysteine
• Hyperhomocysteinemia (chemically induced, complications, drug therapy)
• Ibuprofen
• Inflammation (complications, drug therapy)
• Male
• Oxidative Stress (physiology)
• Rats
• Rats, Wistar
• Rivastigmine (pharmacology, therapeutic use)
• Synapsins (metabolism)