Premium
Regulation of the postnatal development of dopamine neurons of the substantia nigra in vivo by Akt/protein kinase B
Author(s) -
Ries Vincent,
Cheng HsiaoChun,
Baohan Amy,
Kareva Tatyana,
Oo Tinmarla F.,
Rzhetskaya Margarita,
Bland Ross J.,
During Matthew J.,
Kholodilov Nikolai,
Burke Robert E.
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06101.x
Subject(s) - protein kinase b , biology , neuroscience , striatum , neurotrophin , neurotrophic factors , substantia nigra , neuron , microbiology and biotechnology , dopamine , signal transduction , receptor , dopaminergic , biochemistry
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.