SIRT1 Regulates Dendritic Development in Hippocampal Neurons

Juan F. Codocedo, Claudio Allard, Juan A. Godoy, Lorena Varela-Nallar, Nibaldo C. Inestrosa

Resultado de la investigación: Article

41 Citas (Scopus)

Resumen

Dendritic arborization is required for proper neuronal connectivity. SIRT1, a NAD+ dependent histone deacetylase, has been associated to ageing and longevity, which in neurons is linked to neuronal differentiation and neuroprotection. In the present study, the role of SIRT1 in dendritic development was evaluated in cultured hippocampal neurons which were transfected at 3 days in vitro with a construct coding for SIRT1 or for the dominant negative SIRT1H363Y, which lacks the catalytic activity. Neurons overexpressing SIRT1 showed an increased dendritic arborization, while neurons overexpressing SIRT1H363Y showed a reduction in dendritic arbor complexity. The effect of SIRT1 was mimicked by treatment with resveratrol, a well known activator of SIRT1, which has no effect in neurons overexpressing SIRT1H363Y indicating that the effect of resveratrol was specifically mediated by SIRT1. Moreover, hippocampal neurons overexpressing SIRT1 were resistant to dendritic dystrophy induced by Aβ aggregates, an effect that was dependent on the deacetylase activity of SIRT1. Our findings indicate that SIRT1 plays a role in the development and maintenance of dendritic branching in hippocampal neurons, and suggest that these effects are mediated by the ROCK signaling pathway.

Idioma originalEnglish
Número de artículoe47073
PublicaciónPLoS ONE
Volumen7
N.º10
DOI
EstadoPublished - 4 oct 2012

Huella dactilar

Neurons
neurons
Neuronal Plasticity
resveratrol
histone deacetylase
Histone Deacetylases
catalytic activity
NAD
branching
Catalyst activity
Aging of materials
Maintenance

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Citar esto

Codocedo, J. F., Allard, C., Godoy, J. A., Varela-Nallar, L., & Inestrosa, N. C. (2012). SIRT1 Regulates Dendritic Development in Hippocampal Neurons. PLoS ONE, 7(10), [e47073]. https://doi.org/10.1371/journal.pone.0047073
Codocedo, Juan F. ; Allard, Claudio ; Godoy, Juan A. ; Varela-Nallar, Lorena ; Inestrosa, Nibaldo C. / SIRT1 Regulates Dendritic Development in Hippocampal Neurons. En: PLoS ONE. 2012 ; Vol. 7, N.º 10.
@article{7f4074e51f1a45709f8f6b415107fc55,
title = "SIRT1 Regulates Dendritic Development in Hippocampal Neurons",
abstract = "Dendritic arborization is required for proper neuronal connectivity. SIRT1, a NAD+ dependent histone deacetylase, has been associated to ageing and longevity, which in neurons is linked to neuronal differentiation and neuroprotection. In the present study, the role of SIRT1 in dendritic development was evaluated in cultured hippocampal neurons which were transfected at 3 days in vitro with a construct coding for SIRT1 or for the dominant negative SIRT1H363Y, which lacks the catalytic activity. Neurons overexpressing SIRT1 showed an increased dendritic arborization, while neurons overexpressing SIRT1H363Y showed a reduction in dendritic arbor complexity. The effect of SIRT1 was mimicked by treatment with resveratrol, a well known activator of SIRT1, which has no effect in neurons overexpressing SIRT1H363Y indicating that the effect of resveratrol was specifically mediated by SIRT1. Moreover, hippocampal neurons overexpressing SIRT1 were resistant to dendritic dystrophy induced by Aβ aggregates, an effect that was dependent on the deacetylase activity of SIRT1. Our findings indicate that SIRT1 plays a role in the development and maintenance of dendritic branching in hippocampal neurons, and suggest that these effects are mediated by the ROCK signaling pathway.",
author = "Codocedo, {Juan F.} and Claudio Allard and Godoy, {Juan A.} and Lorena Varela-Nallar and Inestrosa, {Nibaldo C.}",
year = "2012",
month = "10",
day = "4",
doi = "10.1371/journal.pone.0047073",
language = "English",
volume = "7",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "10",

}

Codocedo, JF, Allard, C, Godoy, JA, Varela-Nallar, L & Inestrosa, NC 2012, 'SIRT1 Regulates Dendritic Development in Hippocampal Neurons', PLoS ONE, vol. 7, n.º 10, e47073. https://doi.org/10.1371/journal.pone.0047073

SIRT1 Regulates Dendritic Development in Hippocampal Neurons. / Codocedo, Juan F.; Allard, Claudio; Godoy, Juan A.; Varela-Nallar, Lorena; Inestrosa, Nibaldo C.

En: PLoS ONE, Vol. 7, N.º 10, e47073, 04.10.2012.

Resultado de la investigación: Article

TY - JOUR

T1 - SIRT1 Regulates Dendritic Development in Hippocampal Neurons

AU - Codocedo, Juan F.

AU - Allard, Claudio

AU - Godoy, Juan A.

AU - Varela-Nallar, Lorena

AU - Inestrosa, Nibaldo C.

PY - 2012/10/4

Y1 - 2012/10/4

N2 - Dendritic arborization is required for proper neuronal connectivity. SIRT1, a NAD+ dependent histone deacetylase, has been associated to ageing and longevity, which in neurons is linked to neuronal differentiation and neuroprotection. In the present study, the role of SIRT1 in dendritic development was evaluated in cultured hippocampal neurons which were transfected at 3 days in vitro with a construct coding for SIRT1 or for the dominant negative SIRT1H363Y, which lacks the catalytic activity. Neurons overexpressing SIRT1 showed an increased dendritic arborization, while neurons overexpressing SIRT1H363Y showed a reduction in dendritic arbor complexity. The effect of SIRT1 was mimicked by treatment with resveratrol, a well known activator of SIRT1, which has no effect in neurons overexpressing SIRT1H363Y indicating that the effect of resveratrol was specifically mediated by SIRT1. Moreover, hippocampal neurons overexpressing SIRT1 were resistant to dendritic dystrophy induced by Aβ aggregates, an effect that was dependent on the deacetylase activity of SIRT1. Our findings indicate that SIRT1 plays a role in the development and maintenance of dendritic branching in hippocampal neurons, and suggest that these effects are mediated by the ROCK signaling pathway.

AB - Dendritic arborization is required for proper neuronal connectivity. SIRT1, a NAD+ dependent histone deacetylase, has been associated to ageing and longevity, which in neurons is linked to neuronal differentiation and neuroprotection. In the present study, the role of SIRT1 in dendritic development was evaluated in cultured hippocampal neurons which were transfected at 3 days in vitro with a construct coding for SIRT1 or for the dominant negative SIRT1H363Y, which lacks the catalytic activity. Neurons overexpressing SIRT1 showed an increased dendritic arborization, while neurons overexpressing SIRT1H363Y showed a reduction in dendritic arbor complexity. The effect of SIRT1 was mimicked by treatment with resveratrol, a well known activator of SIRT1, which has no effect in neurons overexpressing SIRT1H363Y indicating that the effect of resveratrol was specifically mediated by SIRT1. Moreover, hippocampal neurons overexpressing SIRT1 were resistant to dendritic dystrophy induced by Aβ aggregates, an effect that was dependent on the deacetylase activity of SIRT1. Our findings indicate that SIRT1 plays a role in the development and maintenance of dendritic branching in hippocampal neurons, and suggest that these effects are mediated by the ROCK signaling pathway.

UR - http://www.scopus.com/inward/record.url?scp=84867131638&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0047073

DO - 10.1371/journal.pone.0047073

M3 - Article

C2 - 23056585

AN - SCOPUS:84867131638

VL - 7

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 10

M1 - e47073

ER -