The Rho Kinase Inhibitor Fasudil Mitigates Neurocognitive Deficits in D-Galactose-Induced Brain Aging in Rats: Involvement of SIRT1, BDNF and NF-κB | ||||
Bulletin of Egyptian Society for Physiological Sciences | ||||
Volume 45, Issue 1, January 2025, Page 18-31 PDF (1.01 MB) | ||||
Document Type: Review Article | ||||
DOI: 10.21608/besps.2024.324333.1179 | ||||
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Authors | ||||
Suzan A Khodir![]() ![]() ![]() | ||||
1Medical Physiology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt. | ||||
2Histology and Cell Biology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia | ||||
3Medical Biochemistry and Molecular Biology Department, Faculty of medicine, Menoufia University | ||||
4Histology and Cell Biology, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt. | ||||
5Medical Physiology Department, Faculty of Medicine, Suez Canal University | ||||
6Neuropsychiatry Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia | ||||
7Human Anatomy and Embryology, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt. | ||||
8Medical Pharmacology Department, Faculty of medicine, Suez Canal University Ismailia, Egypt | ||||
Abstract | ||||
Abstract Introduction: Cognitive deficits and aging were evoked by D-galactose (D-gal). Fasudil (Fsd) slows the start and progress of neurodegenerative illnesses. Objective: to illustrate the neuroprotective effect of Fsd in D-gal induced cognitive deficits and the underling mechanisms involved Material & methods: Thirty Wister albino male rats divided into control, D-gal, D-gal+Fsd groups. Rats were subjected to MWM, NOR and EPM tests then rats were sacrificed and MDA, catalase, TNF-α, IL-6 hippocampal gene expression of BDNF, SIRT1 and NF-kB were assessed. Histopathological and immunoreaction for caspase-3 and GFAP were done. Results: D-gal revealed cognitive impairment, with substantial elevation of MDA, TNF-α, IL-6 and NF-kB gene expression and significant reduction of catalase, SIRT1 and BDNF gene expression of D-gal with upregulation of caspase-3 and GFAP immunoreaction in hippocampus. Fsd dramatically improved D-gal induced changes. Conclusion: Fsd alleviated D-gal induced cognitive deficits by anti-oxidant, anti-inflammatory, anti-apoptotic mechanisms in addition to up-regulation of Sirt1 and BDNF gene expression and improving gliosis. | ||||
Keywords | ||||
SIRT1; BDNF; GFAP; D-galactose; Fasudil and NF-κB | ||||
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