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

Research output: Contribution to journalArticle

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).

Details

Authors
  • Zuzanna Kurowska
  • Patrik Brundin
  • Martin E Schwab
  • Jia-Yi Li
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences
Original languageEnglish
Pages (from-to)456-466
JournalNeuroscience
Volume256
Publication statusPublished - 2014
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neural Plasticity and Repair (013210080), Neuronal Survival (013212041)