Alam, Sayed Ibrar and Jo, Min Gi and Park, Tae Ju and Ullah, Rahat and Ahmad, Sareer and Rehman, Shafiq Ur and Kim, Myeong Ok (2021) Quinpirole-Mediated Regulation of Dopamine D2 Receptors Inhibits Glial Cell-Induced Neuroinflammation in Cortex and Striatum after Brain Injury. Biomedicines, 9 (1). p. 47. ISSN 2227-9059
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Abstract
Brain injury is a significant risk factor for chronic gliosis and neurodegenerative diseases. Currently, no treatment is available for neuroinflammation caused by the action of glial cells following brain injury. In this study, we investigated the quinpirole-mediated activation of dopamine D2 receptors (D2R) in a mouse model of traumatic brain injury (TBI). We also investigated the neuroprotective effects of quinpirole (a D2R agonist) against glial cell-induced neuroinflammation secondary to TBI in adult mice. After the brain injury, we injected quinpirole into the TBI mice at a dose of 1 mg/kg daily intraperitoneally for 7 days. Our results showed suppression of D2R expression and deregulation of downstream signaling molecules in ipsilateral cortex and striatum after TBI on day 7. Quinpirole administration regulated D2R expression and significantly reduced glial cell-induced neuroinflammation via the D2R/Akt/glycogen synthase kinase 3 beta (GSK3-β) signaling pathway after TBI. Quinpirole treatment concomitantly attenuated increase in glial cells, neuronal apoptosis, synaptic dysfunction, and regulated proteins associated with the blood–brain barrier, together with the recovery of lesion volume in the TBI mouse model. Additionally, our in vitro results confirmed that quinpirole reversed the microglial condition media complex-mediated deleterious effects and regulated D2R levels in HT22 cells. This study showed that quinpirole administration after TBI reduced secondary brain injury-induced glial cell activation and neuroinflammation via regulation of the D2R/Akt/GSK3-β signaling pathways. Our study suggests that quinpirole may be a safe therapeutic agent against TBI-induced neurodegeneration.
Item Type: | Article |
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Subjects: | Euro Archives > Chemical Science |
Depositing User: | Managing Editor |
Date Deposited: | 25 Nov 2022 04:30 |
Last Modified: | 22 Jun 2024 07:54 |
URI: | http://publish7promo.com/id/eprint/514 |