Conference Publication Details
Mandatory Fields
Farrelly L. A., Toulouse A., Yilmazer-Hanke D.
5th Neuroscience Ireland Annual Conference
Effect of Amitriptyline and Sodium Valproate on Neuropeptide Y Expression in the SH-SY5Y cell line.
2010
September
Validated
1
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Optional Fields
University College Dublin
02-SEP-10
03-SEP-10
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We have used human SH-SY5Y cells as a model to investigate the effect of a therapeutic concentration of amitriptyline (AMY) and sodium valproate (VPA) on neuropeptide Y (NPY) expression. NPY is a 36 amino acid neuropeptide found in the brain and autonomic nervous system, which is associated with anxiety, epilepsy, learning and memory, sleep, hunger and circadian rhythms. These physiological effects are mediated at least through five G protein coupled receptors. NPY has recently gained much attention due to its implication as an endogenous antiepileptic and antidepressive agent. Novel evidence has demonstrated altered NPY levels in models of anxiety, depression and epilepsy1. Furthermore, certain drugs with antiepileptic or mood modulating effects, may increase levels of NPY which in turn can reduce anxiety levels or dampen seizures and increase seizure threshold. Hence, accumulating data is pointing to the potential of NPY as a novel and attractive pharmacological treatment for mood and seizure disorders. We have employed immunocytochemical methods to show an increase in NPY peptide expression with VPA 0.6 mM(72 h) (One way ANOVA, p<0.0001) and AMY 630 nm (24 h) (One way ANOVA, p<0.0001) that is independent of a 12-O-tetradecanoylphorbol-13- acetate (TPA) application. Additionally, we also report a further up-regulation with simultaneous TPA 16 nm and drug treatment. The concentrations of applied drugs were not toxic to the cells as confirmed by an MTT assay. Results from immunocytochemistry (n = 12 per group) point to a significant increase of NPY levels following a 72 h VPA 0.6 mM treatment (One way ANOVA, p<0.0001) and a further increase in expression with simultaneous VPA and TPA treatment (Newman- Keuls multiple comparison test p<0.05). Taken together, available data point to a regulation of NPY by VPA and also the potential of the SH-SY5Y cell line as a future model for studying the effects of antidepressive and antiepileptic drugs on NPY expression. These may be novel mechanisms through which VPA is exerting its antiepileptic and antidepressive effects, but the precise signaling pathways have yet to be elucidated. Whether the upregulation of NPY is a direct or indirect effect of VPA/AMY has yet to be clarified.

DOI 10.1007/s11845-011-0690-8
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