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Title: | EFFECTS OF VALPROIC ACID ON EXPRESSION OF THE MELATONIN RECEPTORS MT1 AND MT2, AND THE NEUROTROPHIC FACTORS BDNF AND GDNF IN VIVO |
Authors: | Sathiyapalan, Arani |
Advisor: | Niles, Len Foster, Jane Sakic, Boris |
Department: | Medical Sciences (Neuroscience and Behavioral Science) |
Keywords: | Valproic acid;melatonin;melatonin receptors;GDNF;BDNF;HDAC inhibitor;epigenetic;in vivo;Molecular and Cellular Neuroscience;Neuroscience and Neurobiology;Molecular and Cellular Neuroscience |
Publication Date: | Apr-2013 |
Abstract: | <p>Valproic acid (VPA) is clinically utilized as an anti-convulsant and mood stabilizer, though its mechanism of action has not been fully elucidated.<strong> </strong>Evidence suggests an interaction between VPA and the melatonergic system as VPA up-regulated the melatonin MT<sub>1</sub> receptor subtype in rat C6 glioma cells. To determine if the observed effects can translate to an <em>in vivo </em>model, we investigated the effects of chronic VPA administration in a rat model on the expression of MT<sub>1</sub> and MT<sub>2</sub> receptors in the hippocampus. We also investigated the effect of chronic VPA treatment on the expression of the neurotrophic factors BDNF and GDNF in the rat hippocampus and striatum.</p> <p>(1) Animals were separated into two groups with the experimental group receiving VPA (4 mg/mL) for 17 days, and the control receiving vehicle. The hippocampus was dissected and MT<sub>1</sub>, MT<sub>2</sub>, BDNF and GDNF mRNA were analyzed with RT-PCR. (2) Animals were separated into three groups with the first group receiving VPA (4 mg/mL), the second receiving VPA (3 mg/mL) for 16 days, and the control receiving vehicle. MT<sub>2</sub> mRNA in the hippocampal subregions were analyzed with in situ hybridization.</p> <p>VPA induced the expression of MT<sub>1</sub> and MT<sub>2</sub> mRNA in the hippocampus in the experimental group compared to the control group. VPA also increased MT<sub>2</sub> mRNA expression in the subregions of the hippocampus. Additionally, BDNF and GDNF mRNA expression were increased in the VPA treatment group.</p> <p>These findings raise the interesting question of whether the diverse clinical effects of VPA involve an interaction with the melatonergic system.</p> |
URI: | http://hdl.handle.net/11375/12901 |
Identifier: | opendissertations/7748 8807 3995577 |
Appears in Collections: | Open Access Dissertations and Theses |
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