By Mikyas Telahun, Meah Katz, Kristy Bagley

Faculty Mentor: Dr. Deborah O’Dell

Abstract

Neuroinflammation, driven by proinflammatory cytokines, is linked to Alzheimer’s Disease (AD). Norepinephrine (NE) activates microglial adrenergic receptors, potentially increasing IL-1B production. This study investigates the effects of chromic NE exposure on IL-1β production in human microglial cells, using receptor-specific antagonists (prazosin for a1-AR, Yohimbine α2-AR, propranolol for B-AR, and labetalol for both β1-AR and α1-AR) to isolate the effects of α1-AR, β1-AR , and combined receptor pathways. Microglia were treated with antagonists and exposed to medium (1 μM) and high (10 μM) NE concentration. Media was collected at 3, 6 and 9 days, and protein content was standardized using a BSA curve after concentrating samples to 10 μg/ml and performing a 1:30 dilution. IL-1β levels were quantified via ELISA. Based on the standard IL-1β curve, the IL-1β concentration was averaged at 1.215 (+0.02) pg/mL, with the highest levels (4.410 pg/mL) observed under medium NE exposure combined with no treatment. These results suggest blocking β-adrenergic receptors with propranolol induces compensatory activation of α1-adrenergic receptors or other unknown pathways, leading to increased IL-1β production. High NE treatments resulted in higher levels of IL-1β. The lowest levels of IL-1β were seen when both the α and β adrenergic receptors were blocked. These findings highlight the role of adrenergic receptor pathways in modulating IL-1β production and suggest that targeting specific adrenergic receptors may provide therapeutic strategies to mitigate stress-induced neuroinflammation and slow Alzheimer’s disease progression.