Hippocampal SPARC regulates depression-related behavior

SPARC (secreted protein acidic and rich in cysteine) is a matricellular protein highly expressed during development, reorganization and tissue repair. In the central nervous system, glial cells express SPARC during development and in neurogenic regions of the adult brain. Astrocytes control the glut...

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Autores principales:	Campolongo, M., Benedetti, L., Podhajcer, O.L., Pitossi, F., Depino, A.M.
Formato:	JOUR
Materias:	Anxiety-related behavior c-Fos Knockout mouse Neurogenesis Neuronal activity SPARC adenovirus vector osteonectin SPARC protein, mouse animal experiment anxiety disorder article behavior disorder cell proliferation dentate gyrus depression forced swimming test hippocampus maze test mouse nervous system development nonhuman oncogene c fos phenotype priority journal protein expression regulatory mechanism stereotactic procedure age animal anxiety female genetics knockout mouse male pathophysiology Mus Age Factors Animals Anxiety Cell Proliferation Dentate Gyrus Depression Female Hippocampus Male Mice Mice, Knockout Osteonectin Phenotype
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_16011848_v11_n8_p966_Campolongo
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_16011848_v11_n8_p966_Campolongo
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spelling	todo:paper_16011848_v11_n8_p966_Campolongo2023-10-03T16:27:48Z Hippocampal SPARC regulates depression-related behavior Campolongo, M. Benedetti, L. Podhajcer, O.L. Pitossi, F. Depino, A.M. Anxiety-related behavior c-Fos Knockout mouse Neurogenesis Neuronal activity SPARC adenovirus vector osteonectin osteonectin SPARC protein, mouse animal experiment anxiety disorder article behavior disorder cell proliferation dentate gyrus depression forced swimming test hippocampus maze test mouse nervous system development nonhuman oncogene c fos phenotype priority journal protein expression regulatory mechanism stereotactic procedure age animal anxiety depression female genetics hippocampus knockout mouse male pathophysiology Mus Age Factors Animals Anxiety Cell Proliferation Dentate Gyrus Depression Female Hippocampus Male Mice Mice, Knockout Neurogenesis Osteonectin Phenotype SPARC (secreted protein acidic and rich in cysteine) is a matricellular protein highly expressed during development, reorganization and tissue repair. In the central nervous system, glial cells express SPARC during development and in neurogenic regions of the adult brain. Astrocytes control the glutamate receptor levels in the developing hippocampus through SPARC secretion. To further characterize the role of SPARC in the brain, we analyzed the hippocampal-dependent adult behavior of SPARC KO mice. We found that SPARC KOmice show increased levels of anxiety-related behaviors and reduced levels of depression-related behaviors. The antidepressant-like phenotype could be rescued by adenoviral vector-mediated expression of SPARC in the adult hippocampus, but anxiety-related behavior persisted in these mice. To identify the cellular mechanisms underlying these behavioral alterations, we analyzed neuronal activity and neurogenesis in the dentate gyrus (DG). SPARC KO mice have increased levels of neuronal activity, evidenced as more neurons that express c-Fos after a footshock. SPARC also affects cell proliferation in the subgranular zone of the DG, although it does not affect maturation and survival of new neurons. SPARC expression in the adult DGdoes not revert the proliferation phenotype in KO mice, but our results suggest a role of SPARC in limiting the survival of new neurons in the DG. This work suggests that SPARC could affect anxiety-related behavior by modulating neuronal activity, and that depression-related behavior is dependent upon the adult expression of SPARC, which affects adult brain function by mechanisms that need to be elucidated. © 2012 The Authors Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society. Fil:Benedetti, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Podhajcer, O.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Depino, A.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_16011848_v11_n8_p966_Campolongo
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Anxiety-related behavior c-Fos Knockout mouse Neurogenesis Neuronal activity SPARC adenovirus vector osteonectin osteonectin SPARC protein, mouse animal experiment anxiety disorder article behavior disorder cell proliferation dentate gyrus depression forced swimming test hippocampus maze test mouse nervous system development nonhuman oncogene c fos phenotype priority journal protein expression regulatory mechanism stereotactic procedure age animal anxiety depression female genetics hippocampus knockout mouse male pathophysiology Mus Age Factors Animals Anxiety Cell Proliferation Dentate Gyrus Depression Female Hippocampus Male Mice Mice, Knockout Neurogenesis Osteonectin Phenotype
spellingShingle	Anxiety-related behavior c-Fos Knockout mouse Neurogenesis Neuronal activity SPARC adenovirus vector osteonectin osteonectin SPARC protein, mouse animal experiment anxiety disorder article behavior disorder cell proliferation dentate gyrus depression forced swimming test hippocampus maze test mouse nervous system development nonhuman oncogene c fos phenotype priority journal protein expression regulatory mechanism stereotactic procedure age animal anxiety depression female genetics hippocampus knockout mouse male pathophysiology Mus Age Factors Animals Anxiety Cell Proliferation Dentate Gyrus Depression Female Hippocampus Male Mice Mice, Knockout Neurogenesis Osteonectin Phenotype Campolongo, M. Benedetti, L. Podhajcer, O.L. Pitossi, F. Depino, A.M. Hippocampal SPARC regulates depression-related behavior
topic_facet	Anxiety-related behavior c-Fos Knockout mouse Neurogenesis Neuronal activity SPARC adenovirus vector osteonectin osteonectin SPARC protein, mouse animal experiment anxiety disorder article behavior disorder cell proliferation dentate gyrus depression forced swimming test hippocampus maze test mouse nervous system development nonhuman oncogene c fos phenotype priority journal protein expression regulatory mechanism stereotactic procedure age animal anxiety depression female genetics hippocampus knockout mouse male pathophysiology Mus Age Factors Animals Anxiety Cell Proliferation Dentate Gyrus Depression Female Hippocampus Male Mice Mice, Knockout Neurogenesis Osteonectin Phenotype
description	SPARC (secreted protein acidic and rich in cysteine) is a matricellular protein highly expressed during development, reorganization and tissue repair. In the central nervous system, glial cells express SPARC during development and in neurogenic regions of the adult brain. Astrocytes control the glutamate receptor levels in the developing hippocampus through SPARC secretion. To further characterize the role of SPARC in the brain, we analyzed the hippocampal-dependent adult behavior of SPARC KO mice. We found that SPARC KOmice show increased levels of anxiety-related behaviors and reduced levels of depression-related behaviors. The antidepressant-like phenotype could be rescued by adenoviral vector-mediated expression of SPARC in the adult hippocampus, but anxiety-related behavior persisted in these mice. To identify the cellular mechanisms underlying these behavioral alterations, we analyzed neuronal activity and neurogenesis in the dentate gyrus (DG). SPARC KO mice have increased levels of neuronal activity, evidenced as more neurons that express c-Fos after a footshock. SPARC also affects cell proliferation in the subgranular zone of the DG, although it does not affect maturation and survival of new neurons. SPARC expression in the adult DGdoes not revert the proliferation phenotype in KO mice, but our results suggest a role of SPARC in limiting the survival of new neurons in the DG. This work suggests that SPARC could affect anxiety-related behavior by modulating neuronal activity, and that depression-related behavior is dependent upon the adult expression of SPARC, which affects adult brain function by mechanisms that need to be elucidated. © 2012 The Authors Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.
format	JOUR
author	Campolongo, M. Benedetti, L. Podhajcer, O.L. Pitossi, F. Depino, A.M.
author_facet	Campolongo, M. Benedetti, L. Podhajcer, O.L. Pitossi, F. Depino, A.M.
author_sort	Campolongo, M.
title	Hippocampal SPARC regulates depression-related behavior
title_short	Hippocampal SPARC regulates depression-related behavior
title_full	Hippocampal SPARC regulates depression-related behavior
title_fullStr	Hippocampal SPARC regulates depression-related behavior
title_full_unstemmed	Hippocampal SPARC regulates depression-related behavior
title_sort	hippocampal sparc regulates depression-related behavior
url	http://hdl.handle.net/20.500.12110/paper_16011848_v11_n8_p966_Campolongo
work_keys_str_mv	AT campolongom hippocampalsparcregulatesdepressionrelatedbehavior AT benedettil hippocampalsparcregulatesdepressionrelatedbehavior AT podhajcerol hippocampalsparcregulatesdepressionrelatedbehavior AT pitossif hippocampalsparcregulatesdepressionrelatedbehavior AT depinoam hippocampalsparcregulatesdepressionrelatedbehavior
_version_	1807318416894197760

Hippocampal SPARC regulates depression-related behavior

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