• Neuroscience · Jan 2025

    Dopamine-D2-agonist targets mitochondrial dysfunction via diminishing Drp1 mediated fission and normalizing PGC1-α/SIRT3 pathways in a rodent model of Subarachnoid haemorrhage.

    • Ahmed Shaney Rehman, Pravir Kumar, and Suhel Parvez.
    • Department of Medical Elementology & Toxicology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India.
    • Neuroscience. 2025 Jan 9; 564: 607860-78.

    AbstractThe adverse impact of disturbmitochondrialbiogenesis onearly brain injury (EBI) following subarachnoid haemorrhage (SAH) has been broadly recognized and is closely associated with oxidative stress and neuronal apoptosis. Previous studies have indicated the therapeutic potential of Ropinirole, a dopamine D2 agonist, in Ischemic Stroke. However, there is a lack of evidence regarding the ability of Ropinirole to enhance mitochondrial biogenesis and quality control after subarachnoid haemorrhage. The objective of this study is to investigate the effects of Ropinirole specific doses (10 & 20 mg/kg b. wt.) on mitochondria dysfunction in endovascular perforation SAH model in male Wistar rat. An endovascular perforation model was established using male Wistar rats that had sustained SAH injury. After the SAH injury, SAH grading on blood clot, Nissl staining, and neurobehavioral assessment were used to determine the severity. ROS and MMP, which are indicators of oxidative stress, were examined using flow cytometry. The findings demonstrated that the use of Ropinirole improved neurobehavioral outcomes, decreased brain edema, and reduced oxidative stress and mitochondrial based apoptosis. Further research showed that, Ropinirole therapy inhibit Drp1-mediated fission by accelerating the activity of fusion protein Mfn2/OPA1 along with regulating the translocation of PGC1-α and SIRT3 through restricting cytochrome C inside mitochondria to maintain mitochondrial metabolism. Ropinirole exerted neuroprotective effects by improving mitochondrial activity in a PGC1-α/SIRT3-dependent way via regulating Drp1 mediated fission. The effective treatment for SAH-induced EBI may involve increasing biogenesis and inhibiting excessive mitochondrial fission with Ropinirole.Copyright © 2024. Published by Elsevier Inc.

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