Association of N-cadherin levels and downstream effectors of Rho GTPases with dendritic spine loss induced by chronic stress in rat hippocampal neurons

Patricia Castañeda, Mauricio Muñoz, Gonzalo García-Rojo, José L. Ulloa, Javier A. Bravo, Ruth Márquez, M. Alexandra García-Pérez, Damaris Arancibia, Karina Araneda, Paulina S. Rojas, David Mondaca-Ruff, Gabriela Díaz-Véliz, Sergio Mora, Esteban Aliaga, Jenny L. Fiedler

Resultado de la investigación: Article

24 Citas (Scopus)

Resumen

Chronic stress promotes cognitive impairment and dendritic spine loss in hippocampal neurons. In this animal model of depression, spine loss probably involves a weakening of the interaction between pre- and postsynaptic cell adhesion molecules, such as N-cadherin, followed by disruption of the cytoskeleton. N-cadherin, in concert with catenin, stabilizes the cytoskeleton through Rho-family GTPases. Via their effector LIM kinase (LIMK), RhoA and ras-related C3 botulinum toxin substrate 1 (RAC) GTPases phosphorylate and inhibit cofilin, an actin-depolymerizing molecule, favoring spine growth. Additionally, RhoA, through Rho kinase (ROCK), inactivates myosin phosphatase through phosphorylation of the myosin-binding subunit (MYPT1), producing actomyosin contraction and probable spine loss. Some micro-RNAs negatively control the translation of specific mRNAs involved in Rho GTPase signaling. For example, miR-138 indirectly activates RhoA, and miR-134 reduces LIMK1 levels, resulting in spine shrinkage; in contrast, miR-132 activates RAC1, promoting spine formation. We evaluated whether N-cadherin/β-catenin and Rho signaling is sensitive to chronic restraint stress. Stressed rats exhibit anhedonia, impaired associative learning, and immobility in the forced swim test and reduction in N-cadherin levels but not β-catenin in the hippocampus. We observed a reduction in spine number in the apical dendrites of CA1 pyramidal neurons, with no effect on the levels of miR-132 or miR-134. Although the stress did not modify the RAC-LIMK-cofilin signaling pathway, we observed increased phospho-MYPT1 levels, probably mediated by RhoA-ROCK activation. Furthermore, chronic stress raises the levels of miR-138 in accordance with the observed activation of the RhoA-ROCK pathway. Our findings suggest that a dysregulation of RhoA-ROCK activity by chronic stress could potentially underlie spine loss in hippocampal neurons.

Idioma originalEnglish
Páginas (desde-hasta)1476-1491
Número de páginas16
PublicaciónJournal of Neuroscience Research
Volumen93
N.º10
DOI
EstadoPublished - 1 oct 2015

Huella dactilar

rho GTP-Binding Proteins
Dendritic Spines
Cadherins
Spine
Neurons
Catenins
Lim Kinases
Actin Depolymerizing Factors
Cytoskeleton
rac1 GTP-Binding Protein
Myosin-Light-Chain Phosphatase
Anhedonia
Actomyosin
rho-Associated Kinases
Pyramidal Cells
GTP Phosphohydrolases
Cell Adhesion Molecules
Protein Biosynthesis
Myosins
Dendrites

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Citar esto

Castañeda, Patricia ; Muñoz, Mauricio ; García-Rojo, Gonzalo ; Ulloa, José L. ; Bravo, Javier A. ; Márquez, Ruth ; García-Pérez, M. Alexandra ; Arancibia, Damaris ; Araneda, Karina ; Rojas, Paulina S. ; Mondaca-Ruff, David ; Díaz-Véliz, Gabriela ; Mora, Sergio ; Aliaga, Esteban ; Fiedler, Jenny L. / Association of N-cadherin levels and downstream effectors of Rho GTPases with dendritic spine loss induced by chronic stress in rat hippocampal neurons. En: Journal of Neuroscience Research. 2015 ; Vol. 93, N.º 10. pp. 1476-1491.
@article{8392968d3d8840c7a97dc420f86f5c4f,
title = "Association of N-cadherin levels and downstream effectors of Rho GTPases with dendritic spine loss induced by chronic stress in rat hippocampal neurons",
abstract = "Chronic stress promotes cognitive impairment and dendritic spine loss in hippocampal neurons. In this animal model of depression, spine loss probably involves a weakening of the interaction between pre- and postsynaptic cell adhesion molecules, such as N-cadherin, followed by disruption of the cytoskeleton. N-cadherin, in concert with catenin, stabilizes the cytoskeleton through Rho-family GTPases. Via their effector LIM kinase (LIMK), RhoA and ras-related C3 botulinum toxin substrate 1 (RAC) GTPases phosphorylate and inhibit cofilin, an actin-depolymerizing molecule, favoring spine growth. Additionally, RhoA, through Rho kinase (ROCK), inactivates myosin phosphatase through phosphorylation of the myosin-binding subunit (MYPT1), producing actomyosin contraction and probable spine loss. Some micro-RNAs negatively control the translation of specific mRNAs involved in Rho GTPase signaling. For example, miR-138 indirectly activates RhoA, and miR-134 reduces LIMK1 levels, resulting in spine shrinkage; in contrast, miR-132 activates RAC1, promoting spine formation. We evaluated whether N-cadherin/β-catenin and Rho signaling is sensitive to chronic restraint stress. Stressed rats exhibit anhedonia, impaired associative learning, and immobility in the forced swim test and reduction in N-cadherin levels but not β-catenin in the hippocampus. We observed a reduction in spine number in the apical dendrites of CA1 pyramidal neurons, with no effect on the levels of miR-132 or miR-134. Although the stress did not modify the RAC-LIMK-cofilin signaling pathway, we observed increased phospho-MYPT1 levels, probably mediated by RhoA-ROCK activation. Furthermore, chronic stress raises the levels of miR-138 in accordance with the observed activation of the RhoA-ROCK pathway. Our findings suggest that a dysregulation of RhoA-ROCK activity by chronic stress could potentially underlie spine loss in hippocampal neurons.",
keywords = "AB_10708808, AB_1642257, AB_228307, AB_228341, AB_2491619, AB_260391, AB_330238, AB_398236, AB_476743, AB_634603, Behavior, Depression, N-cadherin, Resource ID, RGD_70508, Rho proteins, RRID, RRID: AB_1031185, RRID: rid_000081, SCR_013725, SCR_013726, Stress, β-catenin",
author = "Patricia Casta{\~n}eda and Mauricio Mu{\~n}oz and Gonzalo Garc{\'i}a-Rojo and Ulloa, {Jos{\'e} L.} and Bravo, {Javier A.} and Ruth M{\'a}rquez and Garc{\'i}a-P{\'e}rez, {M. Alexandra} and Damaris Arancibia and Karina Araneda and Rojas, {Paulina S.} and David Mondaca-Ruff and Gabriela D{\'i}az-V{\'e}liz and Sergio Mora and Esteban Aliaga and Fiedler, {Jenny L.}",
year = "2015",
month = "10",
day = "1",
doi = "10.1002/jnr.23602",
language = "English",
volume = "93",
pages = "1476--1491",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "10",

}

Castañeda, P, Muñoz, M, García-Rojo, G, Ulloa, JL, Bravo, JA, Márquez, R, García-Pérez, MA, Arancibia, D, Araneda, K, Rojas, PS, Mondaca-Ruff, D, Díaz-Véliz, G, Mora, S, Aliaga, E & Fiedler, JL 2015, 'Association of N-cadherin levels and downstream effectors of Rho GTPases with dendritic spine loss induced by chronic stress in rat hippocampal neurons', Journal of Neuroscience Research, vol. 93, n.º 10, pp. 1476-1491. https://doi.org/10.1002/jnr.23602

Association of N-cadherin levels and downstream effectors of Rho GTPases with dendritic spine loss induced by chronic stress in rat hippocampal neurons. / Castañeda, Patricia; Muñoz, Mauricio; García-Rojo, Gonzalo; Ulloa, José L.; Bravo, Javier A.; Márquez, Ruth; García-Pérez, M. Alexandra; Arancibia, Damaris; Araneda, Karina; Rojas, Paulina S.; Mondaca-Ruff, David; Díaz-Véliz, Gabriela; Mora, Sergio; Aliaga, Esteban; Fiedler, Jenny L.

En: Journal of Neuroscience Research, Vol. 93, N.º 10, 01.10.2015, p. 1476-1491.

Resultado de la investigación: Article

TY - JOUR

T1 - Association of N-cadherin levels and downstream effectors of Rho GTPases with dendritic spine loss induced by chronic stress in rat hippocampal neurons

AU - Castañeda, Patricia

AU - Muñoz, Mauricio

AU - García-Rojo, Gonzalo

AU - Ulloa, José L.

AU - Bravo, Javier A.

AU - Márquez, Ruth

AU - García-Pérez, M. Alexandra

AU - Arancibia, Damaris

AU - Araneda, Karina

AU - Rojas, Paulina S.

AU - Mondaca-Ruff, David

AU - Díaz-Véliz, Gabriela

AU - Mora, Sergio

AU - Aliaga, Esteban

AU - Fiedler, Jenny L.

PY - 2015/10/1

Y1 - 2015/10/1

N2 - Chronic stress promotes cognitive impairment and dendritic spine loss in hippocampal neurons. In this animal model of depression, spine loss probably involves a weakening of the interaction between pre- and postsynaptic cell adhesion molecules, such as N-cadherin, followed by disruption of the cytoskeleton. N-cadherin, in concert with catenin, stabilizes the cytoskeleton through Rho-family GTPases. Via their effector LIM kinase (LIMK), RhoA and ras-related C3 botulinum toxin substrate 1 (RAC) GTPases phosphorylate and inhibit cofilin, an actin-depolymerizing molecule, favoring spine growth. Additionally, RhoA, through Rho kinase (ROCK), inactivates myosin phosphatase through phosphorylation of the myosin-binding subunit (MYPT1), producing actomyosin contraction and probable spine loss. Some micro-RNAs negatively control the translation of specific mRNAs involved in Rho GTPase signaling. For example, miR-138 indirectly activates RhoA, and miR-134 reduces LIMK1 levels, resulting in spine shrinkage; in contrast, miR-132 activates RAC1, promoting spine formation. We evaluated whether N-cadherin/β-catenin and Rho signaling is sensitive to chronic restraint stress. Stressed rats exhibit anhedonia, impaired associative learning, and immobility in the forced swim test and reduction in N-cadherin levels but not β-catenin in the hippocampus. We observed a reduction in spine number in the apical dendrites of CA1 pyramidal neurons, with no effect on the levels of miR-132 or miR-134. Although the stress did not modify the RAC-LIMK-cofilin signaling pathway, we observed increased phospho-MYPT1 levels, probably mediated by RhoA-ROCK activation. Furthermore, chronic stress raises the levels of miR-138 in accordance with the observed activation of the RhoA-ROCK pathway. Our findings suggest that a dysregulation of RhoA-ROCK activity by chronic stress could potentially underlie spine loss in hippocampal neurons.

AB - Chronic stress promotes cognitive impairment and dendritic spine loss in hippocampal neurons. In this animal model of depression, spine loss probably involves a weakening of the interaction between pre- and postsynaptic cell adhesion molecules, such as N-cadherin, followed by disruption of the cytoskeleton. N-cadherin, in concert with catenin, stabilizes the cytoskeleton through Rho-family GTPases. Via their effector LIM kinase (LIMK), RhoA and ras-related C3 botulinum toxin substrate 1 (RAC) GTPases phosphorylate and inhibit cofilin, an actin-depolymerizing molecule, favoring spine growth. Additionally, RhoA, through Rho kinase (ROCK), inactivates myosin phosphatase through phosphorylation of the myosin-binding subunit (MYPT1), producing actomyosin contraction and probable spine loss. Some micro-RNAs negatively control the translation of specific mRNAs involved in Rho GTPase signaling. For example, miR-138 indirectly activates RhoA, and miR-134 reduces LIMK1 levels, resulting in spine shrinkage; in contrast, miR-132 activates RAC1, promoting spine formation. We evaluated whether N-cadherin/β-catenin and Rho signaling is sensitive to chronic restraint stress. Stressed rats exhibit anhedonia, impaired associative learning, and immobility in the forced swim test and reduction in N-cadherin levels but not β-catenin in the hippocampus. We observed a reduction in spine number in the apical dendrites of CA1 pyramidal neurons, with no effect on the levels of miR-132 or miR-134. Although the stress did not modify the RAC-LIMK-cofilin signaling pathway, we observed increased phospho-MYPT1 levels, probably mediated by RhoA-ROCK activation. Furthermore, chronic stress raises the levels of miR-138 in accordance with the observed activation of the RhoA-ROCK pathway. Our findings suggest that a dysregulation of RhoA-ROCK activity by chronic stress could potentially underlie spine loss in hippocampal neurons.

KW - AB_10708808

KW - AB_1642257

KW - AB_228307

KW - AB_228341

KW - AB_2491619

KW - AB_260391

KW - AB_330238

KW - AB_398236

KW - AB_476743

KW - AB_634603

KW - Behavior

KW - Depression

KW - N-cadherin

KW - Resource ID

KW - RGD_70508

KW - Rho proteins

KW - RRID

KW - RRID: AB_1031185

KW - RRID: rid_000081

KW - SCR_013725

KW - SCR_013726

KW - Stress

KW - β-catenin

UR - http://www.scopus.com/inward/record.url?scp=84939473760&partnerID=8YFLogxK

U2 - 10.1002/jnr.23602

DO - 10.1002/jnr.23602

M3 - Article

C2 - 26010004

AN - SCOPUS:84939473760

VL - 93

SP - 1476

EP - 1491

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 10

ER -