Adipocytokine signaling is altered in flinders sensitive line rats, and adiponectin correlates in humans with some symptoms of depression

Clare J. Wilhelm; Dongseok Choi; Marilyn Huckans; Laura Manthe; Jennifer M. Loftis

doi:10.1016/j.pbb.2012.11.001

Adipocytokine signaling is altered in flinders sensitive line rats, and adiponectin correlates in humans with some symptoms of depression

Clare J. Wilhelm
, Dongseok Choi
, Marilyn Huckans
, Laura Manthe
, Jennifer M. Loftis

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

Major depression is a complex multi-factorial disorder with a lifetime diagnosis of nearly 1 out of 6. We used the Flinders Sensitive Line (FSL) of rats, a model of depression, and the parent Sprague-Dawley (SD) rats to identify genes, gene ontology categories and pathways associated with depression. Depression-like behavior was verified in the FSL line by forced swim testing, with FSL animals exhibiting greater immobility compared to SD rats. RNA samples from the hippocampus were isolated from a group of experimentally naïve FSL and SD rats for microarray analysis. Microarray analysis yielded a total of 361 genes that were differentially regulated between FSL and SD rats, with catechol-O-methyltransferase (COMT) being the most up-regulated. The genes that were differentially regulated between FSL and SD rats were subjected to bioinformatic analysis using the Database for Annotation, Visualization and Integrated Discovery (DAVID), which yielded several gene ontology categories that were overrepresented. Subsequent pathway analysis indicated dysregulation of the adipocytokine signaling pathway. To test the translational impact of this pathway, metabolic factors and psychiatric symptoms were evaluated in a sample of human research participants. Results from our human subjects indicated that anxiety and a subset of depressive symptoms were correlated with adiponectin levels (but not leptin levels). Our results and those of others suggest that disruption of the adipocytokine signaling pathway may be a critical component of the depressive-like behaviors observed in the FSL rats and may also be an important indicator of depressive and anxiety symptoms in humans.

Original language	English (US)
Pages (from-to)	643-651
Number of pages	9
Journal	Pharmacology Biochemistry and Behavior
Volume	103
Issue number	3
DOIs	https://doi.org/10.1016/j.pbb.2012.11.001
State	Published - Jan 2013

Funding

This material is the result of work supported with resources and the use of facilities at the Portland Veterans Affairs Medical Center . JML, CJW and MH are supported by career development awards from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and Clinical Sciences Research and Development . We thank Dr. Amir H. Rezvani, Department of Psychiatry, Duke University Medical Center for providing the Flinders Sensitive Line rats and Dr. David Overstreet, Department of Psychiatry, University of North Carolina at Chapel Hill, for review of this manuscript. We also thank Nikki Walter and the Portland Alcohol Research Center Molecular and Bioinformatics Core for technical assistance with the quantitative real-time PCR.

Funders	Funder number
Veterans Health Administration
U.S. Department of Veterans Affairs	I01BX002061
Office of Research and Development Clinical Research and Development Program

Keywords

Adipocytokine
Behavioral despair
Depression
Forced swim test
Hippocampus
Keywords

ASJC Scopus subject areas

Biochemistry
Toxicology
Pharmacology
Clinical Biochemistry
Biological Psychiatry
Behavioral Neuroscience

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10.1016/j.pbb.2012.11.001

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title = "Adipocytokine signaling is altered in flinders sensitive line rats, and adiponectin correlates in humans with some symptoms of depression",

abstract = "Major depression is a complex multi-factorial disorder with a lifetime diagnosis of nearly 1 out of 6. We used the Flinders Sensitive Line (FSL) of rats, a model of depression, and the parent Sprague-Dawley (SD) rats to identify genes, gene ontology categories and pathways associated with depression. Depression-like behavior was verified in the FSL line by forced swim testing, with FSL animals exhibiting greater immobility compared to SD rats. RNA samples from the hippocampus were isolated from a group of experimentally na{\"i}ve FSL and SD rats for microarray analysis. Microarray analysis yielded a total of 361 genes that were differentially regulated between FSL and SD rats, with catechol-O-methyltransferase (COMT) being the most up-regulated. The genes that were differentially regulated between FSL and SD rats were subjected to bioinformatic analysis using the Database for Annotation, Visualization and Integrated Discovery (DAVID), which yielded several gene ontology categories that were overrepresented. Subsequent pathway analysis indicated dysregulation of the adipocytokine signaling pathway. To test the translational impact of this pathway, metabolic factors and psychiatric symptoms were evaluated in a sample of human research participants. Results from our human subjects indicated that anxiety and a subset of depressive symptoms were correlated with adiponectin levels (but not leptin levels). Our results and those of others suggest that disruption of the adipocytokine signaling pathway may be a critical component of the depressive-like behaviors observed in the FSL rats and may also be an important indicator of depressive and anxiety symptoms in humans.",

keywords = "Adipocytokine, Behavioral despair, Depression, Forced swim test, Hippocampus, Keywords",

author = "Wilhelm, \{Clare J.\} and Dongseok Choi and Marilyn Huckans and Laura Manthe and Loftis, \{Jennifer M.\}",

note = "Funding Information: This material is the result of work supported with resources and the use of facilities at the Portland Veterans Affairs Medical Center . JML, CJW and MH are supported by career development awards from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and Clinical Sciences Research and Development . We thank Dr. Amir H. Rezvani, Department of Psychiatry, Duke University Medical Center for providing the Flinders Sensitive Line rats and Dr. David Overstreet, Department of Psychiatry, University of North Carolina at Chapel Hill, for review of this manuscript. We also thank Nikki Walter and the Portland Alcohol Research Center Molecular and Bioinformatics Core for technical assistance with the quantitative real-time PCR. ",

year = "2013",

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doi = "10.1016/j.pbb.2012.11.001",

language = "English (US)",

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AU - Huckans, Marilyn

AU - Manthe, Laura

AU - Loftis, Jennifer M.

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PY - 2013/1

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N2 - Major depression is a complex multi-factorial disorder with a lifetime diagnosis of nearly 1 out of 6. We used the Flinders Sensitive Line (FSL) of rats, a model of depression, and the parent Sprague-Dawley (SD) rats to identify genes, gene ontology categories and pathways associated with depression. Depression-like behavior was verified in the FSL line by forced swim testing, with FSL animals exhibiting greater immobility compared to SD rats. RNA samples from the hippocampus were isolated from a group of experimentally naïve FSL and SD rats for microarray analysis. Microarray analysis yielded a total of 361 genes that were differentially regulated between FSL and SD rats, with catechol-O-methyltransferase (COMT) being the most up-regulated. The genes that were differentially regulated between FSL and SD rats were subjected to bioinformatic analysis using the Database for Annotation, Visualization and Integrated Discovery (DAVID), which yielded several gene ontology categories that were overrepresented. Subsequent pathway analysis indicated dysregulation of the adipocytokine signaling pathway. To test the translational impact of this pathway, metabolic factors and psychiatric symptoms were evaluated in a sample of human research participants. Results from our human subjects indicated that anxiety and a subset of depressive symptoms were correlated with adiponectin levels (but not leptin levels). Our results and those of others suggest that disruption of the adipocytokine signaling pathway may be a critical component of the depressive-like behaviors observed in the FSL rats and may also be an important indicator of depressive and anxiety symptoms in humans.

AB - Major depression is a complex multi-factorial disorder with a lifetime diagnosis of nearly 1 out of 6. We used the Flinders Sensitive Line (FSL) of rats, a model of depression, and the parent Sprague-Dawley (SD) rats to identify genes, gene ontology categories and pathways associated with depression. Depression-like behavior was verified in the FSL line by forced swim testing, with FSL animals exhibiting greater immobility compared to SD rats. RNA samples from the hippocampus were isolated from a group of experimentally naïve FSL and SD rats for microarray analysis. Microarray analysis yielded a total of 361 genes that were differentially regulated between FSL and SD rats, with catechol-O-methyltransferase (COMT) being the most up-regulated. The genes that were differentially regulated between FSL and SD rats were subjected to bioinformatic analysis using the Database for Annotation, Visualization and Integrated Discovery (DAVID), which yielded several gene ontology categories that were overrepresented. Subsequent pathway analysis indicated dysregulation of the adipocytokine signaling pathway. To test the translational impact of this pathway, metabolic factors and psychiatric symptoms were evaluated in a sample of human research participants. Results from our human subjects indicated that anxiety and a subset of depressive symptoms were correlated with adiponectin levels (but not leptin levels). Our results and those of others suggest that disruption of the adipocytokine signaling pathway may be a critical component of the depressive-like behaviors observed in the FSL rats and may also be an important indicator of depressive and anxiety symptoms in humans.

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KW - Behavioral despair

KW - Depression

KW - Forced swim test

KW - Hippocampus

KW - Keywords

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JO - Pharmacology Biochemistry and Behavior

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IS - 3

ER -

Adipocytokine signaling is altered in flinders sensitive line rats, and adiponectin correlates in humans with some symptoms of depression

Abstract

Funding

Keywords

ASJC Scopus subject areas

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