title: Regulation of the postnatal development of dopamine neurons of the substantia nigra in vivo by Akt/protein kinase B.
abstract: Following mitosis, specification and migration during embryogenesis, dopamine neurons of the mesencephalon undergo a postnatal naturally occurring cell death event that determines their final adult number, and a period of axonal growth that determines pattern and extent of target contacts. While a number of neurotrophic factors have been suggested to regulate these developmental events, little is known, especially in vivo, of the cell signaling pathways that mediate these effects. We have examined the possible role of Akt/Protein Kinase B by transduction of these neurons in vivo with adeno-associated viral vectors to express either a constitutively active or a dominant negative form of Akt/protein kinase B. We find that Akt regulates multiple features of the postnatal development of these neurons, including the magnitude of the apoptotic developmental cell death event, neuron size, and the extent of target innervation of the striatum. Given the diversity and magnitude of its effects, the regulation of the development of these neurons by Akt may have implications for the many psychiatric and neurologic diseases in which these neurons may play a role.
authors.affiliation: Klinik für Neurologie, Universitätsklinikum Giessen und Marburg GmbH, Marburg, Germany.
authors.forename: Vincent
authors.initials: V
authors.lastname: Ries
authors.forename: Hsiao-Chun
authors.initials: HC
authors.lastname: Cheng
authors.forename: Amy
authors.initials: A
authors.lastname: Baohan
authors.forename: Tatyana
authors.initials: T
authors.lastname: Kareva
authors.forename: Tinmarla F
authors.initials: TF
authors.lastname: Oo
authors.forename: Margarita
authors.initials: M
authors.lastname: Rzhetskaya
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Bland
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: During
authors.forename: Nikolai
authors.initials: N
authors.lastname: Kholodilov
authors.forename: Robert E
authors.initials: RE
authors.lastname: Burke
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D048429:Cell Size; D004298:Dopamine / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics; D020439:Growth Cones / Q000201:enzymology / Q000648:ultrastructure; D007150:Immunohistochemistry; D008297:Male; D009434:Neural Pathways / Q000166:cytology / Q000201:enzymology / Q000254:growth & development; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D014161:Transduction, Genetic / Q000379:methods
chemical_list: D051057:Proto-Oncogene Proteins c-akt; D004298:Dopamine