Paroxetine is Pro-inflammatory in Human Brain Microvascular Endothelial Cells

BACKGROUND: Paroxetine is an antidepressant that is widely used. However, Paroxetine possesses anticholinergic properties which may contribute to cognitive decline in older adults. Surprisingly, the mechanisms of the cognitive decline of anticholinergic drugs in older adults remains elusive. A hypothesis is that a loss of cholinergic signaling is pro-inflammatory in the brain. We designed experiments to determine if Paroxetine is pro-inflammatory in Normal Human Brain Microvascular Endothelial Cells (NHBMECs). METHOD: NHBMECs were grown at 5% CO2, 37C and 95% relative humidity until 90% confluent. NHBMECs were treated with the RNA free water as control, Paroxetine as 1.67x 10 4 mM/mol, IL1B 2ng/ml for 24 hours. RNA was isolated, converted into CDNA, and gene expression determined via RT-PCR. Statistical analysis was performed via ANOVA and post-hoc Tukey’s with a significant p-value \u3c 0.05. Experiments were completed on 10-04-19. The mRNA expression studies were performed on 11-01-19. RESULTS: NHBMECs exposed to Paroxetine for 24 hours demonstrated elevated expression of CCL2 and CXCL5. NHBMECs exposed to Paroxetine + IL1B demonstrated synergistic elevations in CCL2 and CXCL5. CONCLUSION: Our result suggests that Paroxetine may have pro-inflammatory properties within this subset of human brain cells. Therefore, our preliminary data suggests the possibility of pathological pro- inflammatory mechanisms associated with Paroxetine. Further evaluation of different populations of normal human brain cells are warranted.https://scholarscompass.vcu.edu/gradposters/1096/thumbnail.jp