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Modulating Mitochondrial Dynamics Mitigates Cognitive Impairment in Rats with Myocardial Infarction.
- Source :
-
Current neuropharmacology [Curr Neuropharmacol] 2024; Vol. 22 (10), pp. 1749-1760. - Publication Year :
- 2024
-
Abstract
- Background: We have previously demonstrated that oxidative stress and brain mitochondrial dysfunction are key mediators of brain pathology during myocardial infarction (MI).<br />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.<br />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.<br />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.<br />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.<br /> (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Subjects :
- Animals
Male
Rats
Quinazolinones pharmacology
Mitochondria drug effects
Mitochondria metabolism
Blood-Brain Barrier drug effects
Blood-Brain Barrier metabolism
Brain metabolism
Brain drug effects
Angiotensin-Converting Enzyme Inhibitors pharmacology
Mitochondrial Dynamics drug effects
Cognitive Dysfunction drug therapy
Cognitive Dysfunction metabolism
Cognitive Dysfunction etiology
Myocardial Infarction metabolism
Myocardial Infarction drug therapy
Myocardial Infarction complications
Oxidative Stress drug effects
Enalapril pharmacology
Rats, Sprague-Dawley
Subjects
Details
- Language :
- English
- ISSN :
- 1875-6190
- Volume :
- 22
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Current neuropharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 38362882
- Full Text :
- https://doi.org/10.2174/1570159X22666240131114913