Fatty acids increase neuronal hypertrophy of Pten knockdown neurons

Catherine J. Fricano, Tyrone DeSpenza, Paul W. Frazel, Meijie Li, A. James O'Malley, Gary L. Westbrook, Bryan W. Luikart

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Phosphatase and tensin homolog (Pten) catalyzes the reverse reaction of PI3K by dephosphorylating PIP3 to PIP2. This negatively regulates downstream Akt/mTOR/S6 signaling resulting in decreased cellular growth and proliferation. Co-injection of a lentivirus knocking Pten down with a control lentivirus allows us to compare the effects of Pten knockdown between individual neurons within the same animal. We find that knockdown of Pten results in neuronal hypertrophy by 21 days post-injection. This neuronal hypertrophy is correlated with increased p-S6 and p-mTOR in individual neurons. We used this system to test whether an environmental factor that has been implicated in cellular hypertrophy could influence the severity of the Pten knockdown-induced hypertrophy. Implantation of mini-osmotic pumps delivering fatty acids results in increased neuronal hypertrophy and p-S6/p-mTOR staining. These hypertrophic effects were reversed in response to rapamycin treatment. However, we did not observe a similar increase in hypertrophy in response to dietary manipulations of fatty acids. Thus, we conclude that by driving growth signaling with fatty acids and knocking down a critical regulator of growth, Pten, we are able to observe an additive morphological phenotype of increased soma size mediated by the mTOR pathway.

Original languageEnglish (US)
Article number30
JournalFrontiers in Molecular Neuroscience
Volume7
Issue number1 APR
DOIs
StatePublished - Apr 23 2014

Keywords

  • Fatty acids
  • Neuronal hypertrophy
  • PI3K
  • Pten
  • Rapamycin
  • mTOR
  • pS6

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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  • Cite this

    Fricano, C. J., DeSpenza, T., Frazel, P. W., Li, M., James O'Malley, A., Westbrook, G. L., & Luikart, B. W. (2014). Fatty acids increase neuronal hypertrophy of Pten knockdown neurons. Frontiers in Molecular Neuroscience, 7(1 APR), [30]. https://doi.org/10.3389/fnmol.2014.00030