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Gene expression changes in the septum: possible implications for microRNAs in sculpting the maternal brain.

Zhao C, Saul MC, Driessen T, Gammie SC - PLoS ONE (2012)

Bottom Line: These genes were previously found to be differentially regulated in other brain regions during lactation.Unexpectedly, enrichment analysis revealed a high number of microRNAs, transcription factors, or conserved binding sites (177 with corrected P-value <0.05) that were significantly linked to maternal upregulated genes, while none were linked to downregulated genes.Together, this study provides new insights into genes (along with possible mechanisms for their regulation) that are involved in septum-mediated adaptations during the postpartum period.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America. czhao23@wisc.edu

ABSTRACT
The transition from the non-maternal to the maternal state is characterized by a variety of CNS alterations that support the care of offspring. The septum (including lateral and medial portions) is a brain region previously linked to various emotional and motivational processes, including maternal care. In this study, we used microarrays (PLIER algorithm) to examine gene expression changes in the septum of postpartum mice and employed gene set enrichment analysis (GSEA) to identify possible regulators of altered gene expression. Genes of interest identified as differentially regulated with microarray analysis were validated with quantitative real-time PCR. We found that fatty acid binding protein 7 (Fabp7) and galanin (Gal) were downregulated, whereas insulin-like growth factor binding protein 3 (Igfbp3) was upregulated in postpartum mice compared to virgin females. These genes were previously found to be differentially regulated in other brain regions during lactation. We also identified altered expression of novel genes not previously linked to maternal behavior, but that could play a role in postpartum processes, including glutamate-ammonia ligase (Glul) and somatostatin receptor 1 (Sstr1) (both upregulated in postpartum). Genes implicated in metabolism, cell differentiation, or proliferation also exhibited altered expression. Unexpectedly, enrichment analysis revealed a high number of microRNAs, transcription factors, or conserved binding sites (177 with corrected P-value <0.05) that were significantly linked to maternal upregulated genes, while none were linked to downregulated genes. MicroRNAs have been linked to placenta and mammary gland development, but this is the first indication they may also play a key role in sculpting the maternal brain. Together, this study provides new insights into genes (along with possible mechanisms for their regulation) that are involved in septum-mediated adaptations during the postpartum period.

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Quantitative real-time PCR analysis of Fabp7, Gal, Glul, Igfbp3, Npy1r and Sstr1 expression in the septum.Relative expression distribution of mRNA (y-axis) represented as a ratio of maternal versus virgin mice, was calculated using Ywhaz and CycA as reference genes, and shown by box-and-whisker plot as medians (dashed lines), interquartile range (boxes) and ranges (whiskers). Ratios over one indicate genes with higher expression in maternal relative to virgin mice, and ratios of less than one indicate genes with lower expression in maternal as opposed to virgin mice. Confirming array results, postpartum mice exhibited increased Glul, Igfbp3, Sstr1and decreased Fabp7 and Gal mRNA levels relative to virgin control mice. Npy1 was not confirmed. *P<0.05 maternal mice versus virgin control.
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pone-0038602-g001: Quantitative real-time PCR analysis of Fabp7, Gal, Glul, Igfbp3, Npy1r and Sstr1 expression in the septum.Relative expression distribution of mRNA (y-axis) represented as a ratio of maternal versus virgin mice, was calculated using Ywhaz and CycA as reference genes, and shown by box-and-whisker plot as medians (dashed lines), interquartile range (boxes) and ranges (whiskers). Ratios over one indicate genes with higher expression in maternal relative to virgin mice, and ratios of less than one indicate genes with lower expression in maternal as opposed to virgin mice. Confirming array results, postpartum mice exhibited increased Glul, Igfbp3, Sstr1and decreased Fabp7 and Gal mRNA levels relative to virgin control mice. Npy1 was not confirmed. *P<0.05 maternal mice versus virgin control.

Mentions: Consistent with the findings from microarray analysis, mRNA levels of three representative genes, Glul (P = 0.023), Igfbp3 (P = 0.004) and Sstr1 (P = 0.048) were identified as being significantly up-regulated in maternal mice as compared to virgin mice, whereas Fabp7 (P<0.001) and Gal (P = 0.023) were significantly down-regulated (Fig. 1). While Npy1r mRNA levels were found to be significantly increased in lactating versus virgin mice in the microarray analysis, we did not confirm a difference between the two groups using highly sensitive real-time PCR technique (Fig. 1).


Gene expression changes in the septum: possible implications for microRNAs in sculpting the maternal brain.

Zhao C, Saul MC, Driessen T, Gammie SC - PLoS ONE (2012)

Quantitative real-time PCR analysis of Fabp7, Gal, Glul, Igfbp3, Npy1r and Sstr1 expression in the septum.Relative expression distribution of mRNA (y-axis) represented as a ratio of maternal versus virgin mice, was calculated using Ywhaz and CycA as reference genes, and shown by box-and-whisker plot as medians (dashed lines), interquartile range (boxes) and ranges (whiskers). Ratios over one indicate genes with higher expression in maternal relative to virgin mice, and ratios of less than one indicate genes with lower expression in maternal as opposed to virgin mice. Confirming array results, postpartum mice exhibited increased Glul, Igfbp3, Sstr1and decreased Fabp7 and Gal mRNA levels relative to virgin control mice. Npy1 was not confirmed. *P<0.05 maternal mice versus virgin control.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3368935&req=5

pone-0038602-g001: Quantitative real-time PCR analysis of Fabp7, Gal, Glul, Igfbp3, Npy1r and Sstr1 expression in the septum.Relative expression distribution of mRNA (y-axis) represented as a ratio of maternal versus virgin mice, was calculated using Ywhaz and CycA as reference genes, and shown by box-and-whisker plot as medians (dashed lines), interquartile range (boxes) and ranges (whiskers). Ratios over one indicate genes with higher expression in maternal relative to virgin mice, and ratios of less than one indicate genes with lower expression in maternal as opposed to virgin mice. Confirming array results, postpartum mice exhibited increased Glul, Igfbp3, Sstr1and decreased Fabp7 and Gal mRNA levels relative to virgin control mice. Npy1 was not confirmed. *P<0.05 maternal mice versus virgin control.
Mentions: Consistent with the findings from microarray analysis, mRNA levels of three representative genes, Glul (P = 0.023), Igfbp3 (P = 0.004) and Sstr1 (P = 0.048) were identified as being significantly up-regulated in maternal mice as compared to virgin mice, whereas Fabp7 (P<0.001) and Gal (P = 0.023) were significantly down-regulated (Fig. 1). While Npy1r mRNA levels were found to be significantly increased in lactating versus virgin mice in the microarray analysis, we did not confirm a difference between the two groups using highly sensitive real-time PCR technique (Fig. 1).

Bottom Line: These genes were previously found to be differentially regulated in other brain regions during lactation.Unexpectedly, enrichment analysis revealed a high number of microRNAs, transcription factors, or conserved binding sites (177 with corrected P-value <0.05) that were significantly linked to maternal upregulated genes, while none were linked to downregulated genes.Together, this study provides new insights into genes (along with possible mechanisms for their regulation) that are involved in septum-mediated adaptations during the postpartum period.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America. czhao23@wisc.edu

ABSTRACT
The transition from the non-maternal to the maternal state is characterized by a variety of CNS alterations that support the care of offspring. The septum (including lateral and medial portions) is a brain region previously linked to various emotional and motivational processes, including maternal care. In this study, we used microarrays (PLIER algorithm) to examine gene expression changes in the septum of postpartum mice and employed gene set enrichment analysis (GSEA) to identify possible regulators of altered gene expression. Genes of interest identified as differentially regulated with microarray analysis were validated with quantitative real-time PCR. We found that fatty acid binding protein 7 (Fabp7) and galanin (Gal) were downregulated, whereas insulin-like growth factor binding protein 3 (Igfbp3) was upregulated in postpartum mice compared to virgin females. These genes were previously found to be differentially regulated in other brain regions during lactation. We also identified altered expression of novel genes not previously linked to maternal behavior, but that could play a role in postpartum processes, including glutamate-ammonia ligase (Glul) and somatostatin receptor 1 (Sstr1) (both upregulated in postpartum). Genes implicated in metabolism, cell differentiation, or proliferation also exhibited altered expression. Unexpectedly, enrichment analysis revealed a high number of microRNAs, transcription factors, or conserved binding sites (177 with corrected P-value <0.05) that were significantly linked to maternal upregulated genes, while none were linked to downregulated genes. MicroRNAs have been linked to placenta and mammary gland development, but this is the first indication they may also play a key role in sculpting the maternal brain. Together, this study provides new insights into genes (along with possible mechanisms for their regulation) that are involved in septum-mediated adaptations during the postpartum period.

Show MeSH