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The Effect of Amitriptyline on Biomarkers Associated with Brain Health and Drug Metabolism
Ashana Jackson, Dept. of Psychology, Bukola Odeniyi, and Omar Hassan, with Dr. Elvin T. Price, VCU School of Pharmacy
High anticholinergic drugs, like amitriptyline have been linked to dementia and other neurodegenerative diseases. Chronic use of high doses of amitriptyline can lead to a decrease in brain capabilities and even negative effects on short-term memory. Expression of different brain biomarkers are also linked to various cognitive decline: Decreased expressions of PPARG and CREB1 have been correlated with a decrease in the brain’s ability to protect against aging, and impaired spatial memory, respectively. Increased expression of CACNA1C has been negatively correlated with short term object recognition. Therefore, the study examined the effect of amitriptyline on brain biomarkers: CACNA1C, CREB1, and PPARG. Human astrocytes were grown and separated into three 6-well sample plates. Cell treatment groups were: ILB, Amitriptyline 50M, Amitriptyline 220M, ILB + Amitriptyline 50M and ILB + Amitriptyline 220M. The mRNA expression was measured using RT-PCR. The data was analyzed by graph pad prism and ANOVA with Sidak’s multiple comparison’s test.After exposure of astrocytes to both concentrations of amitriptyline, there was increased expression of the CANA1C and decreased PPARG. Exposure to 220M amitriptyline lead to decreased expression of CREB1, but amitriptyline at 50M lead to an increase in expression. Findings indicated that amitriptyline significantly increased expression and decreased expression of PPARG. Though, different concentrations had varying effects on CREB1. These results indicate that the cognitive decline linked to amitriptyline are likely the effects that this drug has on these genes.
Elvin T. Price, Pharm.D., Ph.D.
Virginia Commonwealth University. Undergraduate Research Opportunities Program
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