Title:Modulating Mitochondrial Dynamics Mitigates Cognitive Impairment in
Rats with Myocardial Infarction
Volume: 22
Issue: 10
Author(s): Kewarin Jinawong, Chanon Piamsiri, Nattayaporn Apaijai, Chayodom Maneechote, Busarin Arunsak, Wichwara Nawara, Chanisa Thonusin, Hiranya Pintana, Nipon Chattipakorn and Siriporn C. Chattipakorn*
Affiliation:
- Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai
University, Chiang Mai 50200, Thailand
- Center of Excellence in Cardiac Electrophysiology Research, Chiang
Mai University, Chiang Mai 50200, Thailand
- Department of Oral Biology and Diagnostic Sciences,
Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand
Keywords:
Myocardial infarction, cognitive impairment, brain metabolism, mitochondrial fission, mitochondrial fusion, mitochondrial dysfunction.
Abstract:
Background: We have previously demonstrated that oxidative stress and brain mitochondrial
dysfunction are key mediators of brain pathology during myocardial infarction (MI).
Objective: To investigate the beneficial effects of mitochondrial dynamic modulators, including mitochondrial
fission inhibitor (Mdivi-1) and mitochondrial fusion promotor (M1), on cognitive function
and molecular signaling in the brain of MI rats in comparison with the effect of enalapril.
Methods: Male rats were assigned to either sham or MI operation. In the MI group, rats with an ejection
Fraction less than 50% were included, and then they received one of the following treatments for
5 weeks: vehicle, enalapril, Mdivi-1, or M1. Cognitive function was tested, and the brains were used
for molecular study.
Results: MI rats exhibited cardiac dysfunction with systemic oxidative stress. Cognitive impairment
was found in MI rats, along with dendritic spine loss, blood-brain barrier (BBB) breakdown, brain mitochondrial
dysfunction, and decreased mitochondrial and increased glycolysis metabolism, without
the alteration of APP, BACE-1, Tau and p-Tau proteins. Treatment with Mdivi-1, M1, and enalapril
equally improved cognitive function in MI rats. All treatments decreased dendritic spine loss, brain
mitochondrial oxidative stress, and restored mitochondrial metabolism. Brain mitochondrial fusion
was recovered only in the Mdivi-1-treated group.
Conclusion: Mitochondrial dynamics modulators improved cognitive function in MI rats through a
reduction of systemic oxidative stress and brain mitochondrial dysfunction and the enhancement
of mitochondrial metabolism. In addition, this mitochondrial fission inhibitor increased mitochondrial
fusion in MI rats.
