Nicotinamide reduces dopamine in postnatal hypothalamus and causes dopamine-deficient phenotype.
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.
Lee
Jae-Yong
JY
Department of Biochemistry, College of Medicine, Hallym University, Chuncheon, Gangwon-do 200-702, South Korea.
Ahn
Kyungsook
K
Jang
Bong Geom
BG
Park
Seong-Hoon
SH
Kang
Hong-Jun
HJ
Heo
Jee-In
JI
Ko
Yoon-Jung
YJ
Won
Moo-Ho
MH
Tae-Cheon Kang
Jo
Sangmee Ahn
SA
Kim
Min-Ju
MJ
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
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