By Kristy A. Bagley, Mikyas G. Telahun

Faculty Mentor: Deborah A. O’Dell

Abstract

More than six million Americans are currently living with Alzheimer’s, a condition characterized by cognitive decline and the presence of amyloid β plaques and Tau tangles. However, the sustained activation of the brain’s macrophages, microglia, and other neuroinflammatory markers of the Central Nervous System (CNS) may serve as a link to Alzheimer’s pathology (Wang, et al. 10, June 2015). Microglia modulate their activation based on bidirectional communication with neurons following receptor activation. Proinflammatory cytokines like IL-1α, IL-1β, IL-6, and TNF-α, released by microglia, are believed to contribute to the development of Alzheimer’s Disease (AD) and may be released during pathogen detection, neuroinflammation, and stress (Sugama, et al. 16, Dec. 2019). Microglial β1-adrenergic receptors (β1-AR) and β2-adrenergic receptors (β2-AR) display neurotransmitter activation in response to stress-induced epinephrine released by the adrenal glands. As epinephrine is a neurotransmitter that can traverse the blood-brain barrier and influence microglial function, our research aimed to assess the impact of varying epinephrine exposure levels on microglia, focusing particularly on the production of proinflammatory cytokine IL-1β. Understanding the influence of epinephrine on microglial function is pivotal to discovering the mechanisms underpinning stress-related neurological disorders, including Alzheimer’s disease. Our findings revealed that while epinephrine did not stimulate microglia to produce IL-1β, it potentially triggered the production of other cytokines, as evidenced by the increase in media protein concentration over time. Additionally, we observed heightened microglial proliferation in response to epinephrine, contrary to findings in other systems, suggesting a potential link between stress-induced epinephrine and increased neuroinflammation, which could contribute to AD pathology (Tripathi, B. J., R. C. Tripathi. 6, Dec. 1984). Further investigation is warranted to explore the proliferation of microglia in response to epinephrine and its implications for neuroinflammation and Alzheimer’s disease.

Citations:

Sugama, Shuei, et al. “Stress-Induced Microglial Activation Occurs through β-Adrenergic Receptor: Noradrenaline as a Key Neurotransmitter in Microglial Activation.” Journal of Neuroinflammation, vol. 16, Dec. 2019, p. 266. PubMed Central, https://doi.org/10.1186/s12974-019-1632-z.

Tripathi, B. J., and R. C. Tripathi. 6, Dec. 1984 .“Effect of Epinephrine in Vitro on the Morphology, Phagocytosis, and Mitotic Activity of Human Trabecular Endothelium.” Experimental Eye Research, vol. 39, no. pp. 731–44. PubMed, https://doi.org/10.1016/0014-4835(84)90072-1.

Wang, Wen-Ying, et al. 10, June 2015 . “Role of Pro-Inflammatory Cytokines Released from Microglia in Alzheimer’s Disease.” Annals of Translational Medicine, vol. 3, no. p. 136. PubMed Central, https://doi.org/10.3978/j.issn.2305-5839.2015.03.49.