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Intracellular Nogo-A facilitates initiation of neurite formation in mouse midbrain neurons in vitro.

Kurowska, Zuzanna LU ; Brundin, Patrik LU ; Schwab, Martin E and Li, Jia-Yi LU (2014) In Neuroscience 256. p.456-466
Abstract
Nogo-A is a transmembrane protein originally discovered in myelin, produced by postnatal central nervous system (CNS) oligodendrocytes. Nogo-A induces growth cone collapse and inhibition of axonal growth in the injured adult CNS. In the intact CNS, Nogo-A functions as a negative regulator of growth and plasticity. Nogo-A is also expressed by certain neurons. Neuronal Nogo-A depresses long-term potentiation in hippocampus and modulates neurite adhesion and fasciculation during development in mice. Here we show that Nogo-A is present in neurons derived from human midbrain (LUHMES cell line), as well as in embryonic and postnatal mouse midbrain (dopaminergic) neurons. In LUHMES cells, Nogo-A was upregulated 3-fold upon differentiation and... (More)
Nogo-A is a transmembrane protein originally discovered in myelin, produced by postnatal central nervous system (CNS) oligodendrocytes. Nogo-A induces growth cone collapse and inhibition of axonal growth in the injured adult CNS. In the intact CNS, Nogo-A functions as a negative regulator of growth and plasticity. Nogo-A is also expressed by certain neurons. Neuronal Nogo-A depresses long-term potentiation in hippocampus and modulates neurite adhesion and fasciculation during development in mice. Here we show that Nogo-A is present in neurons derived from human midbrain (LUHMES cell line), as well as in embryonic and postnatal mouse midbrain (dopaminergic) neurons. In LUHMES cells, Nogo-A was upregulated 3-fold upon differentiation and neurite extension. Nogo-A was localized intracellularly in differentiated LUHMES cells. Cultured midbrain (dopaminergic) neurons from Nogo-A knock-out mice exhibited decreased numbers of neurites and branches when compared with neurons from wild type mice. However, this phenotype was not observed when the cultures from wild type mice were treated with an antibody neutralizing plasma membrane Nogo-A. In vivo, neither the regeneration of nigrostriatal tyrosine hydroxylase fibers, nor the survival of nigral dopaminergic neurons after partial 6-hydroxydopamine lesions were affected by Nogo-A deletion. These results indicate that during maturation of cultured midbrain (dopaminergic) neurons, intracellular Nogo-A supports neurite growth initiation and branch formation. Abbreaviations: 6-OHDA, (6-hydroxydopamine); CNS, (central nervous system); DAB, (3,3'-Diaminobenzidine); DAPI, (4',6-diamidino-2-phenylindole); KO, (knock-out); LTP, (long term potentiation); LUHMES cells (Lund University Human Mesencephalon cells); PFA, (paraformaldehyde); SDS-PAGE, (sodium dodecyl sulfate polyacrylamide gel electrophoresis); TH, (tyrosine hydroxylase); WT, (wild type). (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neuroscience
volume
256
pages
456 - 466
publisher
Elsevier
external identifiers
  • pmid:24157929
  • wos:000330485500045
  • scopus:84890022817
ISSN
1873-7544
DOI
10.1016/j.neuroscience.2013.10.029
language
English
LU publication?
yes
id
b78bed8c-20c3-4fb9-bd70-8e5e55e24924 (old id 4143019)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24157929?dopt=Abstract
date added to LUP
2013-11-04 22:23:59
date last changed
2017-09-24 03:23:26
@article{b78bed8c-20c3-4fb9-bd70-8e5e55e24924,
  abstract     = {Nogo-A is a transmembrane protein originally discovered in myelin, produced by postnatal central nervous system (CNS) oligodendrocytes. Nogo-A induces growth cone collapse and inhibition of axonal growth in the injured adult CNS. In the intact CNS, Nogo-A functions as a negative regulator of growth and plasticity. Nogo-A is also expressed by certain neurons. Neuronal Nogo-A depresses long-term potentiation in hippocampus and modulates neurite adhesion and fasciculation during development in mice. Here we show that Nogo-A is present in neurons derived from human midbrain (LUHMES cell line), as well as in embryonic and postnatal mouse midbrain (dopaminergic) neurons. In LUHMES cells, Nogo-A was upregulated 3-fold upon differentiation and neurite extension. Nogo-A was localized intracellularly in differentiated LUHMES cells. Cultured midbrain (dopaminergic) neurons from Nogo-A knock-out mice exhibited decreased numbers of neurites and branches when compared with neurons from wild type mice. However, this phenotype was not observed when the cultures from wild type mice were treated with an antibody neutralizing plasma membrane Nogo-A. In vivo, neither the regeneration of nigrostriatal tyrosine hydroxylase fibers, nor the survival of nigral dopaminergic neurons after partial 6-hydroxydopamine lesions were affected by Nogo-A deletion. These results indicate that during maturation of cultured midbrain (dopaminergic) neurons, intracellular Nogo-A supports neurite growth initiation and branch formation. Abbreaviations: 6-OHDA, (6-hydroxydopamine); CNS, (central nervous system); DAB, (3,3'-Diaminobenzidine); DAPI, (4',6-diamidino-2-phenylindole); KO, (knock-out); LTP, (long term potentiation); LUHMES cells (Lund University Human Mesencephalon cells); PFA, (paraformaldehyde); SDS-PAGE, (sodium dodecyl sulfate polyacrylamide gel electrophoresis); TH, (tyrosine hydroxylase); WT, (wild type).},
  author       = {Kurowska, Zuzanna and Brundin, Patrik and Schwab, Martin E and Li, Jia-Yi},
  issn         = {1873-7544},
  language     = {eng},
  pages        = {456--466},
  publisher    = {Elsevier},
  series       = {Neuroscience},
  title        = {Intracellular Nogo-A facilitates initiation of neurite formation in mouse midbrain neurons in vitro.},
  url          = {http://dx.doi.org/10.1016/j.neuroscience.2013.10.029},
  volume       = {256},
  year         = {2014},
}