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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 it¿s 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.