ArticleJournal of neuroinflammation2025
Exercise-induced irisin ameliorates cognitive impairment following chronic cerebral hypoperfusion by suppressing neuroinflammation and hippocampal neuronal apoptosis.
Article in Journal of neuroinflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed.
- Correlation Between Cognitive Function and Serum Irisin Levels in Parkinson's Disease Patients.Brain and behavior · 2026Article
- Da chuanxiong formula improves vascular remodeling via promoting angiogenesis and vasodilation mediated by PI3K/Akt/eNOS signaling.Metabolic brain disease · 2026Article
- Neuronal Apoptotic Bodies Facilitate Japanese Encephalitis Virus Infection and Pathogenicity.Journal of extracellular vesicles · 2026Article
- Nanomaterial-driven spatiotemporal autophagy modulation: The dual-edged sword in precision cancer therapy.Acta pharmaceutica Sinica. B · 2026Review
- Neuromodulation Techniques in Chronic Cerebral Hypoperfusion: Mechanisms and Therapeutic Advances.CNS neuroscience & therapeutics · 2026Review
- Early Rehabilitation Exercise Promotes Vestibular Compensation in UVN Mice by Regulating Microglial Polarization Balance via the PGC-1α/FNDC5/BDNF Pathway.Molecular neurobiology · 2026Article
- Treadmill exercise relieves cortical interneuron hyperactivation to prevent stress-induced anxiety-like behaviors in male mice.Communications biology · 2026Article
- Genistein-3'-sodium sulfonate improves neuroinflammation, blood-brain barrier function, and microglial activation after chronic cerebral hypoperfusion by regulating TGR5.Metabolic brain disease · 2026Article
- FNDC5/irisin ameliorates diabetes-associated cognitive dysfunction via αVβ5-cAMP signaling to regulate oxidative stress, neuroinflammation and synaptic plasticity.Journal of translational medicine · 2026Article
- Organ-Specific Regulation of Systemic Aging: Focus on the Brain, Skeletal Muscle, and Gut.Cells · 2026Review
- Muscle-brain crosstalk in sarcopenia and cognitive impairment: endocrine signaling, metabolic regulation, and exercise modulation.Frontiers in endocrinology · 2026Review
- Shared Mechanisms in Dementia and Depression: The Modulatory Role of Physical Exercise.Journal of neurochemistry · 2025Review
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12 authors.
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Abstract
backgroundChronic cerebral hypoperfusion (CCH) is a pathophysiological hallmark of vascular dementia, the second most common form of dementia. CCH exerts complex and subtle detrimental effects on both the brain and peripheral systems. Irisin is a polypeptide primarily expressed in contracting skeletal muscle and the brain. However, its role in CCH remains unclear. This study aimed to investigate the effects of CCH on irisin metabolism and whether increasing endogenous irisin levels through forced aerobic exercise (FAE) could confer neuroprotection against secondary brain injury induced by CCH.
methodsA total of 212 adult (8-week-old) male C57BL/6 mice were randomly assigned to either sham or CCH groups. CCH was induced by bilateral common carotid artery stenosis. FAE consisted of daily swimming (1 h/day, 5 days/week, for 5 weeks). Two subgroups of CCH mice received daily intraperitoneal injections of either DMSO or cilengitide trifluoroacetate (CT), a selective inhibitor of integrin αV and β5 (the irisin receptor), during FAE. ELISA and western blotting were used to assess irisin expression, while western blotting, TUNEL, immunofluorescence staining, and neurobehavioral tests were conducted to evaluate neurofunctional outcomes.
resultsHippocampal and serum irisin levels were progressively reduced in CCH mice. Additionally, expression of integrins αV and β5 in hippocampal neurons, microglia, and astrocytes decreased post-CCH. FAE effectively enhanced both peripheral and central irisin expression. Increased endogenous irisin levels inhibited CCH-induced hippocampal neuronal apoptosis and microglial activation, thereby promoting neuronal survival and partially ameliorating white matter injury. These changes led to improvements in memory, motor function, and anxiety- and depression-like behaviors. Mechanistically, the neuroprotective effects of irisin were mediated by enhanced hippocampal neuronal and microglial autophagy through increased AMPK phosphorylation and decreased mTOR phosphorylation-effects abolished by CT treatment.
conclusionOur findings demonstrate that enhancing endogenous irisin via FAE mitigates CCH-induced neuronal apoptosis, microglial activation, cognitive impairment, and affective behavioral deficits by promoting autophagy through the integrin αVβ5/AMPK/mTOR signaling pathway.
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