Quinpirole-mediated regulation of dopamine D2 receptors inhibits glial cell-induced neuroinflammation in cortex and striatum after brain injury

Alam, S. I., Jo, M. G., Park, T. J., Ullah, R., Ahmad, S., Rehman, S. U. and Kim, M. O. (2021) Quinpirole-mediated regulation of dopamine D2 receptors inhibits glial cell-induced neuroinflammation in cortex and striatum after brain injury. Biomedicines, 9(1), 47. (doi: 10.3390/biomedicines9010047) (PMID:33430188) (PMCID:PMC7825629)

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: Articles
• Additional Information: This research was supported by the Neurological Disorder Research Program of the National Research Foundation (NRF) funded by the Korean Government (MSIT) (2020M3E5D9080660).
• Keywords: Brain injury, quinpirole, dopamine D2 receptors, glial cell, neuroinflammation, neurodegeneration.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Park, Tae Ju
• Authors: Alam, S. I., Jo, M. G., Park, T. J., Ullah, R., Ahmad, S., Rehman, S. U., and Kim, M. O.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Biomedicines
• Publisher: MDPI
• ISSN: 2227-9059
• ISSN (Online): 2227-9059
• Published Online: 07 January 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Biomedicines 9(1): 47
• Publisher Policy: Reproduced under a Creative Commons License