Prepubertal Ovariectomy Exaggerates Adult Affective Behaviors and Alters the Hippocampal Transcriptome in a Genetic Rat Model of Depression
Major depressive disorder (MDD) is a debilitating illness that affects twice as many women than men postpuberty. This female bias is thought to be caused by greater heritability of MDD in women and increased vulnerability induced by female sex hormones. We tested this hypothesis by removing the ovar...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-01-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fendo.2017.00373/full |
| _version_ | 1811306838263595008 |
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| author | Neha S. Raghavan Neha S. Raghavan Hao Chen Matthew Schipma Wendy Luo Wendy Luo Sarah Chung Sarah Chung Lei Wang Lei Wang Eva E. Redei Eva E. Redei |
| author_facet | Neha S. Raghavan Neha S. Raghavan Hao Chen Matthew Schipma Wendy Luo Wendy Luo Sarah Chung Sarah Chung Lei Wang Lei Wang Eva E. Redei Eva E. Redei |
| author_sort | Neha S. Raghavan |
| collection | DOAJ |
| description | Major depressive disorder (MDD) is a debilitating illness that affects twice as many women than men postpuberty. This female bias is thought to be caused by greater heritability of MDD in women and increased vulnerability induced by female sex hormones. We tested this hypothesis by removing the ovaries from prepubertal Wistar Kyoto (WKY) more immobile (WMI) females, a genetic animal model of depression, and its genetically close control, the WKY less immobile (WLI). In adulthood, prepubertally ovariectomized (PrePubOVX) animals and their Sham-operated controls were tested for depression- and anxiety-like behaviors, using the routinely employed forced swim and open field tests, respectively, and RNA-sequencing was performed on their hippocampal RNA. Our results confirmed that the behavioral and hippocampal expression changes that occur after prepubertal ovariectomy are the consequences of an interaction between genetic predisposition to depressive behavior and ovarian hormone-regulated processes. Lack of ovarian hormones during and after puberty in the WLIs led to increased depression-like behavior. In WMIs, both depression- and anxiety-like behaviors worsened by prepubertal ovariectomy. The unbiased exploration of the hippocampal transcriptome identified sets of differentially expressed genes (DEGs) between the strains and treatment groups. The relatively small number of hippocampal DEGs resulting from the genetic differences between the strains confirmed the genetic relatedness of these strains. Nevertheless, the differences in DEGs between the strains in response to prepubertal ovariectomy identified different molecular processes, including the importance of glucocorticoid receptor-mediated mechanisms, that may be causative of the increased depression-like behavior in the presence or absence of genetic predisposition. This study contributes to the understanding of hormonal maturation-induced changes in affective behaviors and the hippocampal transcriptome as it relates to genetic predisposition to depression. |
| first_indexed | 2024-04-13T08:53:46Z |
| format | Article |
| id | doaj.art-dd0047e02a144e0680fa69e208f65a3c |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-13T08:53:46Z |
| publishDate | 2018-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-dd0047e02a144e0680fa69e208f65a3c2022-12-22T02:53:25ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922018-01-01810.3389/fendo.2017.00373306407Prepubertal Ovariectomy Exaggerates Adult Affective Behaviors and Alters the Hippocampal Transcriptome in a Genetic Rat Model of DepressionNeha S. Raghavan0Neha S. Raghavan1Hao Chen2Matthew Schipma3Wendy Luo4Wendy Luo5Sarah Chung6Sarah Chung7Lei Wang8Lei Wang9Eva E. Redei10Eva E. Redei11The Asher Center for the Study & Treatment of Depressive Disorders, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDepartment of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDepartment of Pharmacology, The University of Tennessee Health Science Center, Memphis, TN, United StatesNext-Generation Sequencing Core Facility, Northwestern University, Chicago, IL, United StatesThe Asher Center for the Study & Treatment of Depressive Disorders, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDepartment of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesThe Asher Center for the Study & Treatment of Depressive Disorders, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDepartment of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDepartment of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDepartment of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesThe Asher Center for the Study & Treatment of Depressive Disorders, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDepartment of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesMajor depressive disorder (MDD) is a debilitating illness that affects twice as many women than men postpuberty. This female bias is thought to be caused by greater heritability of MDD in women and increased vulnerability induced by female sex hormones. We tested this hypothesis by removing the ovaries from prepubertal Wistar Kyoto (WKY) more immobile (WMI) females, a genetic animal model of depression, and its genetically close control, the WKY less immobile (WLI). In adulthood, prepubertally ovariectomized (PrePubOVX) animals and their Sham-operated controls were tested for depression- and anxiety-like behaviors, using the routinely employed forced swim and open field tests, respectively, and RNA-sequencing was performed on their hippocampal RNA. Our results confirmed that the behavioral and hippocampal expression changes that occur after prepubertal ovariectomy are the consequences of an interaction between genetic predisposition to depressive behavior and ovarian hormone-regulated processes. Lack of ovarian hormones during and after puberty in the WLIs led to increased depression-like behavior. In WMIs, both depression- and anxiety-like behaviors worsened by prepubertal ovariectomy. The unbiased exploration of the hippocampal transcriptome identified sets of differentially expressed genes (DEGs) between the strains and treatment groups. The relatively small number of hippocampal DEGs resulting from the genetic differences between the strains confirmed the genetic relatedness of these strains. Nevertheless, the differences in DEGs between the strains in response to prepubertal ovariectomy identified different molecular processes, including the importance of glucocorticoid receptor-mediated mechanisms, that may be causative of the increased depression-like behavior in the presence or absence of genetic predisposition. This study contributes to the understanding of hormonal maturation-induced changes in affective behaviors and the hippocampal transcriptome as it relates to genetic predisposition to depression.http://journal.frontiersin.org/article/10.3389/fendo.2017.00373/fulldepression-like behaviorWistar Kyoto more immobileforced swim testRNA-Seqdifferentially expressed genes |
| spellingShingle | Neha S. Raghavan Neha S. Raghavan Hao Chen Matthew Schipma Wendy Luo Wendy Luo Sarah Chung Sarah Chung Lei Wang Lei Wang Eva E. Redei Eva E. Redei Prepubertal Ovariectomy Exaggerates Adult Affective Behaviors and Alters the Hippocampal Transcriptome in a Genetic Rat Model of Depression Frontiers in Endocrinology depression-like behavior Wistar Kyoto more immobile forced swim test RNA-Seq differentially expressed genes |
| title | Prepubertal Ovariectomy Exaggerates Adult Affective Behaviors and Alters the Hippocampal Transcriptome in a Genetic Rat Model of Depression |
| title_full | Prepubertal Ovariectomy Exaggerates Adult Affective Behaviors and Alters the Hippocampal Transcriptome in a Genetic Rat Model of Depression |
| title_fullStr | Prepubertal Ovariectomy Exaggerates Adult Affective Behaviors and Alters the Hippocampal Transcriptome in a Genetic Rat Model of Depression |
| title_full_unstemmed | Prepubertal Ovariectomy Exaggerates Adult Affective Behaviors and Alters the Hippocampal Transcriptome in a Genetic Rat Model of Depression |
| title_short | Prepubertal Ovariectomy Exaggerates Adult Affective Behaviors and Alters the Hippocampal Transcriptome in a Genetic Rat Model of Depression |
| title_sort | prepubertal ovariectomy exaggerates adult affective behaviors and alters the hippocampal transcriptome in a genetic rat model of depression |
| topic | depression-like behavior Wistar Kyoto more immobile forced swim test RNA-Seq differentially expressed genes |
| url | http://journal.frontiersin.org/article/10.3389/fendo.2017.00373/full |
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