title: Fatty acids increase neuronal hypertrophy of Pten knockdown neurons.
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.
authors.affiliation: Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth Lebanon, NH, USA.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Fricano
authors.affiliation: Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth Lebanon, NH, USA.
authors.forename: Tyrone
authors.initials: T
authors.lastname: Despenza
authors.affiliation: Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth Lebanon, NH, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Frazel
authors.affiliation: Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth Lebanon, NH, USA.
authors.forename: Meijie
authors.initials: M
authors.lastname: Li
authors.affiliation: The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine at Dartmouth Lebanon, NH, USA.
authors.forename: A James
authors.initials: AJ
authors.lastname: O'Malley
authors.affiliation: The Vollum Institute, Oregon Health and Science University Portland, OR, USA.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Westbrook
authors.affiliation: Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth Lebanon, NH, USA.
authors.forename: Bryan W
authors.initials: BW
authors.lastname: Luikart
keywords: PI3K; Pten; fatty acids; mTOR; neuronal hypertrophy; pS6; rapamycin