title: Dopamine induces apoptosis in young, but not in neonatal, neurons via Ca2+-dependent signal.
abstract: Dopamine signaling plays a major role in regulation of neuronal apoptosis. During the postnatal period, dopamine signaling is known to be dramatically changed in the striatum. However, because it is difficult to culture neurons after birth, little is known about developmental changes in dopamine-mediated apoptosis. To examine such changes, we established the method of primary culture of striatal neurons from 2- to 3-wk-old (young) mice. Dopamine, via D(1)-like receptors, induced apoptosis in young, but not neonatal, striatal neurons, suggesting that the effect of dopamine on apoptosis changed with development. In contrast, although isoproterenol (Iso), a beta-adrenergic receptor agonist, increased cAMP production to a greater degree than dopamine, Iso did not increase apoptosis in striatal neurons from young and neonatal mice, suggesting a minor role of cAMP in dopamine-mediated apoptosis. Next, we examined the effect of dopamine on Ca(2+) signaling. Dopamine, but not Iso, markedly increased intracellular Ca(2+) in striatal neurons from young mice, and Ca(2+)-chelating agents abolished dopamine-induced apoptosis, suggesting that Ca(2+) played a major role in the dopamine-mediated apoptosis pathway. In contrast, dopamine failed to increase intracellular Ca(2+) in neonatal neurons, and the expression of PLC, which can increase intracellular Ca(2+) via D(1)-like receptor activation, was significantly greater in young than in neonatal striatal neurons. These data suggest that the developmental change in dopamine-mediated Ca(2+) signaling was responsible for differences between young and neonatal striatum in induction of apoptosis. Furthermore, the culture of young striatal neurons is feasible and may provide a new tool for developmental studies.
authors.affiliation: Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, New Jersey Medical School-University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA.
authors.forename: Kousaku
authors.initials: K
authors.lastname: Iwatsubo
authors.forename: Sayaka
authors.initials: S
authors.lastname: Suzuki
authors.forename: Chanxia
authors.initials: C
authors.lastname: Li
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsunematsu
authors.forename: Fumi
authors.initials: F
authors.lastname: Nakamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okumura
authors.forename: Motohiko
authors.initials: M
authors.lastname: Sato
authors.forename: Susumu
authors.initials: S
authors.lastname: Minamisawa
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Toya
authors.forename: Satoshi
authors.initials: S
authors.lastname: Umemura
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ishikawa
mesh_terms: D000262:Adenylyl Cyclases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000367:Age Factors; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001479:Basal Ganglia / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D020013:Calcium Signaling / Q000187:drug effects; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005240:Feasibility Studies; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D013997:Time Factors; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism