title: Valproic acid up-regulates melatonin MT1 and MT2 receptors and neurotrophic factors CDNF and MANF in the rat brain.
abstract: We have reported that clinically relevant concentrations of valproic acid (VPA) up-regulate the G-protein-coupled melatonin MT1 receptor in rat C6 glioma cells. To determine whether this effect occurs in vivo, the effects of chronic VPA treatment on the expression of both melatonin receptor subtypes, MT1 and MT2, were examined in the rat brain. Reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR analyses revealed significant increases in MT1 and MT2 mRNA expression in the hippocampus, following VPA (4 mg/ml drinking water) treatment for 17 d. Increases in the mRNA and protein expression of the novel neurotrophic factors, conserved dopamine neurotrophic factor and mesencephalic astrocyte-derived neurotrophic factor, were detected in the hippocampus and/or striatum. In addition, significant changes in persephin, glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor mRNA expression were observed. The robust multi-fold induction of MT1 and MT2 receptors in the hippocampus suggests a role for the melatonergic system in the psychotropic effects of VPA.
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada. niles@mcmaster.ca
authors.forename: Lennard P
authors.initials: LP
authors.lastname: Niles
authors.forename: Arani
authors.initials: A
authors.lastname: Sathiyapalan
authors.forename: Sarra
authors.initials: S
authors.lastname: Bahna
authors.forename: Na Hyea
authors.initials: NH
authors.lastname: Kang
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D044122:Receptor, Melatonin, MT1 / Q000187:drug effects*; D044123:Receptor, Melatonin, MT2 / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; C577430:CDNF protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; C546826:MANF protein, rat; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; C110758:persephin; D014635:Valproic Acid