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Impact of fluoxetine treatment and folic acid supplementation on the mammary gland transcriptome during peak lactation

ABSTRACT: Lactation causes dramatic maternal calcemic adaptations where up to 10% of maternal bone density is mobilized for milk calcium. Serotonin plays a role in regulating this calcemic demand through alterations in DNA methylation. Selective serotonin reuptake inhibitors used to treat peripartum depression exacerbate this signaling. The first objective of this study was to determine the impact of fluoxetine, one of the most popular selective serotonin reuptake inhibitors, on the transcriptome of the mouse mammary gland during peak lactation. The second objective was to determine whether supplementation with folic acid, a well-known methyl donor, would mitigate the gene expression changes induced by fluoxetine.

ORGANISM(S): Mus musculus

PROVIDER: GSE188845 | GEO | 2021/11/22

REPOSITORIES: GEO

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Project description:Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are the most common treatment for major depression. However, approximately 50% of depressed patients fail to achieve an effective treatment response. Understanding how gene expression systems relate to treatment responses may be critical for understanding antidepressant resistance. Transcriptome profiling allows for the simultaneous measurement of expression levels for thousands of genes and the opportunity to utilize this information to determine mechanisms underlying antidepressant treatment responses. However, the best way to relate this immense amount of information to treatment resistance remains unclear. We take a novel approach to this question by examining dentate gyrus transcriptomes from the perspective of a stereotyped fluoxetine-induced gene expression program. Expression programs usually represent stereotyped changes in expression levels that occur as cells transition phenotypes. Fluoxetine will shift transcriptomes so they lie somewhere between a baseline state and a full-response at the end of the program. The position along this fluoxetine-induced gene expression program (program status) was measured using principal components analysis (PCA). The same expression program was initiated in treatment-responsive and resistant mice but treatment response was associated with further progression along the fluoxetine-induced gene expression program. The study of treatment-related differences in gene expression program status represents a novel way to conceptualize differences in treatment responses at a transcriptome level. Understanding how antidepressant-induced gene expression program progression is modulated represents an important area for future research and could guide efforts to develop novel augmentation strategies for antidepressant treatment resistant individuals. 38 samples, 2 dentate regions (dorsal/ventral), 3 groups (control, antidepressant resistant (4 mice), antidepressant responsive (7 mice), untreated (8 mice).

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Impact of fluoxetine treatment and folic acid supplementation on the mammary gland transcriptome during peak lactation

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