Theoretical and Natural Science

- The Open Access Proceedings Series for Conferences


Theoretical and Natural Science

Vol. 32, 06 March 2024


Open Access | Article

Role of dopamine in regulating microglia inflammatory responses through TLR4-NFκb pathway

Miao Zhang * 1
1 High School Affiliated to Renmin University of China

* Author to whom correspondence should be addressed.

Theoretical and Natural Science, Vol. 32, 39-51
Published 06 March 2024. © 2023 The Author(s). Published by EWA Publishing
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Citation Miao Zhang. Role of dopamine in regulating microglia inflammatory responses through TLR4-NFκb pathway. TNS (2024) Vol. 32: 39-51. DOI: 10.54254/2753-8818/32/20240782.

Abstract

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder that affects a significant portion of the population. One of its distinguishing features is the gradual loss of dopaminergic cells in a specific region of the brain known as the substantia nigra. In recent years, researchers have uncovered that neuroinflammation facilitates the developmental process of PD. Specifically, studies have shown that the activation of microglia, the brain’s immune cells, is closely linked to the levels of dopamine secreted by neurons. However, the influence of dopamine on activated microglia in PD has not been fully explored. In this study, we aimed to explore the impact of dopamine on activated microglia. To establish an activated microglia model, we used BV-2 cell lines and treated them with lipopolysaccharide (LPS) at a concentration of 200 ng/ml. Two separate groups were then exposed to dopamine at concentrations of 2 μM and 10 μM, respectively, to simulate dopamine treatment in the brain. To assess the effects of dopamine, we performed real-time PCR to measure the relative mRNA levels of pro- and anti-inflammatory cytokines, conducted immunofluorescent staining to observe and analyze the cell morphology, carried out a phagocytosis assay to assess the cell’s phagocytic ability, and conducted western blotting to identify the specific pathway through which dopamine affects microglia activation. Our findings revealed that dopamine can modulate the activation state of microglia and reduce the cell’s inflammatory responses via the TLR4-NFκB pathway. This suggests that dopamine has the potential to alleviate neuroinflammation in PD, opening up new avenues for future treatments and therapies.

Keywords

Parkinson’s Disease, Neuroinflammation, Microglia, Dopamine

References

1. van Rossum, D., & Hanisch, U.-K. (2004). Microglia. Metabolic brain disease, 19, 393-411.

2. Colonna, M., & Butovsky, O. (2017). Microglia Function in the Central Nervous System During Health and Neurodegeneration. Annual review of immunology, 35(1), 441-468. https://doi.org/10.1146/annurev-immunol-051116-052358

3. Nayak, D., Roth, T. L., & McGavern, D. B. (2014). Microglia development and function. Annual review of immunology, 32, 367-402.

4. Tang, Y., & Le, W. (2016). Differential roles of M1 and M2 microglia in neurodegenerative diseases. Molecular neurobiology, 53, 1181-1194.

5. Samii, A., Nutt, J. G., & Ransom, B. R. (2004). Parkinson’s disease. The Lancet, 363(9423), 1783-1793.

6. Bloem, B. R., Okun, M. S., & Klein, C. (2021). Parkinson’s disease. The Lancet, 397(10291), 2284-2303.

7. Kalia, L. V., & Lang, A. E. (2015). Parkinson’s disease. The Lancet, 386(9996), 896-912.

8. Calne, D. B. (1993). Treatment of Parkinson’s disease. New England Journal of Medicine, 329(14), 1021-1027.

9. Emamzadeh, F. N., & Surguchov, A. (2018). Parkinson’s disease: biomarkers, treatment, and risk factors. Frontiers in neuroscience, 12, 612.

10. Singh, N., Pillay, V., & Choonara, Y. E. (2007). Advances in the treatment of Parkinson’s disease. Progress in neurobiology, 81(1), 29-44.

11. Broome, S. T., Louangaphay, K., Keay, K. A., Leggio, G. M., Musumeci, G., & Castorina, A. (2020). Dopamine: an immune transmitter. Neural regeneration research, 15(12), 2173.

12. Chen, K., Wang, H., Ilyas, I., Mahmood, A., & Hou, L. (2023). Microglia and Astrocytes Dysfunction and Key Neuroinflammation-Based Biomarkers in Parkinson&rsquo’s Disease. Brain Sciences, 13(4), 634. https://www.mdpi.com/2076-3425/13/4/634

13. Huang, Z.-p., Liu, S.-f., Zhuang, J.-l., Li, L.-y., Li, M.-m., Huang, Y.-l., Chen, Y.-h., Chen, X.-r., Lin, S., Ye, L.-c., & Chen, C.-n. (2023). Role of microglial metabolic reprogramming in Parkinson’s disease. Biochemical Pharmacology, 213, 115619. https://doi.org/ 10.1016/j.bcp.2023.115619

14. Albertini, G., Etienne, F., & Roumier, A. (2020). Regulation of microglia by neuromodulators: Modulations in major and minor modes. Neuroscience Letters, 733, 135000. https://doi.org/10.1016/j.neulet.2020.135000

15. Gaskill, P. J., Calderon, T. M., Coley, J. S., & Berman, J. W. (2013). Drug Induced Increases in CNS Dopamine Alter Monocyte, Macrophage and T Cell Functions: Implications for HAND. Journal of Neuroimmune Pharmacology, 8(3), 621-642. https://doi.org/10.1007/s11481-013-9443-y

16. Pinoli, M., Marino, F., & Cosentino, M. (2017). Dopaminergic Regulation of Innate Immunity: a Review. Journal of Neuroimmune Pharmacology, 12(4), 602-623. https://doi.org/10.1007/ s11481-017-9749-2

17. Henn, A., Lund, S., Hedtjärn, M., Schrattenholz, A., Pörzgen, P., & Leist, M. (2009). The suitability of BV2 cells as alternative model system for primary microglia cultures or for animal experiments examining brain inflammation.

18. Haddad, F., Sawalha, M., Khawaja, Y., Najjar, A., & Karaman, R. (2017). Dopamine and levodopa prodrugs for the treatment of Parkinson’s disease. Molecules, 23(1), 40.

19. Perry, V. H., Nicoll, J. A. R., & Holmes, C. (2010). Microglia in neurodegenerative disease. Nature Reviews Neurology, 6(4), 193-201. https://doi.org/10.1038/nrneurol.2010.17

20. An, J., Chen, B., Kang, X., Zhang, R., Guo, Y., Zhao, J., & Yang, H. (2020). Neuroprotective effects of natural compounds on LPS-induced inflammatory responses in microglia. American journal of translational research, 12(6), 2353.

21. Dubbelaar, M. L., Kracht, L., Eggen, B. J. L., & Boddeke, E. W. G. M. (2018). The Kaleidoscope of Microglial Phenotypes [Review]. Frontiers in Immunology, 9. https://doi.org/10.3389/fimmu.2018.01753

22. Eggen, B. J., Raj, D., Hanisch, U.-K., & Boddeke, H. W. (2013). Microglial phenotype and adaptation. Journal of Neuroimmune Pharmacology, 8, 807-823.

23. Gibb, W., & Lees, A. (1988). The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson’s disease. Journal of Neurology, Neurosurgery & Psychiatry, 51(6), 745-752.

24. Butler, C. A., Popescu, A. S., Kitchener, E. J., Allendorf, D. H., Puigdellívol, M., & Brown, G. C. (2021). Microglial phagocytosis of neurons in neurodegeneration, and its regulation. Journal of neurochemistry, 158(3), 621-639.

25. Zhang, W., Wang, T., Pei, Z., Miller, D. S., Wu, X., Block, M. L., Wilson, B., Zhang, W., Zhou, Y., & Hong, J.-S. (2005). Aggregated α‐synuclein activates microglia: a process leading to disease progression in Parkinson’s disease. The FASEB Journal, 19(6), 533-542.

26. Tang, J., Xu, L., Zeng, Y., & Gong, F. (2021). Effect of gut microbiota on LPS-induced acute lung injury by regulating the TLR4/NF-kB signaling pathway. International immunopharmacology, 91, 107272.

27. Yoshioka, Y., Sugino, Y., Shibagaki, F., Yamamuro, A., Ishimaru, Y., & Maeda, S. (2020). Dopamine attenuates lipopolysaccharide-induced expression of proinflammatory cytokines by inhibiting the nuclear translocation of NF-κB p65 through the formation of dopamine quinone in microglia. European Journal of Pharmacology, 866, 172826. https://doi.org/ 10.1016/j.ejphar.2019.172826

28. Brown, A., & Gershon, S. (1993). Dopamine and depression. Journal of Neural Transmission/General Section JNT, 91, 75-109.

Data Availability

The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.

This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License. Authors who publish this series agree to the following terms:

1. Authors retain copyright and grant the series right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this series.

2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the series's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this series.

3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See Open Access Instruction).

Volume Title
Proceedings of the 2nd International Conference on Modern Medicine and Global Health
ISBN (Print)
978-1-83558-321-0
ISBN (Online)
978-1-83558-322-7
Published Date
06 March 2024
Series
Theoretical and Natural Science
ISSN (Print)
2753-8818
ISSN (Online)
2753-8826
DOI
10.54254/2753-8818/32/20240782
Copyright
06 March 2024
Open Access
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Copyright © 2023 EWA Publishing. Unless Otherwise Stated