title: Nicotinamide reduces dopamine in postnatal hypothalamus and causes dopamine-deficient phenotype.
abstract: Dopamine is an important neurotransmitter in the human central nervous system and also plays a key role in the development of postnatal brains. We previously reported that nicotinamide, a SIRT1 inhibitor, regulates tyrosine hydroxylase (TH) expression in vitro. To investigate the effect of nicotinamide-mediated TH regulation in vivo, nicotinamide was chronically injected into neonatal mice. Interestingly, nicotinamide-treated mice were smaller in size, and their locomotor activity was reduced. L-DOPA treatment caused hypersensitive locomotor activity that indicates a dopamine-depleted state. These changes seemed to be associated with dopamine metabolism in hypothalamus, since dopamine in hypothalamus was reduced but not in striatum. The present study suggests that the regulation of dopamine metabolism during the postnatal development is important and the underlying molecular mechanisms may be associated with SIRT1 signaling.
authors.affiliation: Department of Biochemistry, College of Medicine, Hallym University, Chuncheon, Gangwon-do 200-702, South Korea.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Lee
authors.forename: Kyungsook
authors.initials: K
authors.lastname: Ahn
authors.forename: Bong Geom
authors.initials: BG
authors.lastname: Jang
authors.forename: Seong-Hoon
authors.initials: SH
authors.lastname: Park
authors.forename: Hong-Jun
authors.initials: HJ
authors.lastname: Kang
authors.forename: Jee-In
authors.initials: JI
authors.lastname: Heo
authors.forename: Yoon-Jung
authors.initials: YJ
authors.lastname: Ko
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
authors.lastname: Tae-Cheon Kang
authors.forename: Sangmee Ahn
authors.initials: SA
authors.lastname: Jo
authors.forename: Min-Ju
authors.initials: MJ
authors.lastname: Kim
mesh_terms: D000107:Acetylation; D000818:Animals; D000831:Animals, Newborn; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000172:deficiency / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007980:Levodopa / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D009536:Niacinamide / Q000494:pharmacology*; D010641:Phenotype; D056564:Sirtuin 1; D037761:Sirtuins / Q000037:antagonists & inhibitors*; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
chemical_list: D015259:Dopamine Agents; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D009536:Niacinamide; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D037761:Sirtuins; D004298:Dopamine