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Please use this identifier to cite or link to this item: http://hdl.handle.net/10761/1708

Issue Date: 3-Feb-2015
Authors: Seguini, Mara
Title: Analysis of miRNome expression profile in hippocampus of rats treated with antidepressants
Abstract: MicroRNAs (miRNAs) are small, non-coding RNAs with a key role in regulating gene expression at post-transcriptional level. Recent investigations suggested that dysregulation in miRNA expression may be critical for mental disorders pathophysiology, including mood disorders, and in psychotropic drugs action, such as mood stabilizers and antidepressants (ADs). Aim of the studies presented was to analyze whether modulation of hippocampal miRNome could be part of the mode of action of different ADs, fluoxetine, desipramine and agomelatine. Moreover, in order to assess the time course of ADs effects, treatments were performed for various time lengths (3,7 or 21 days). Rat hippocampal miRNome expression was investigated by means of TaqMan Rodent MicroRNA Arrays. We found that all ADs induced a significant modulation of hippocampal miRNome, although with different time-dependent effects. Indeed, all ADs significant modulated miRNA expression already after 3 days of treatment with the most pronounced effect by agomelatine (37 miRNAs, mainly down-regulated); whereas both fluoxetine and desipramine modified the expression of 8 different miRNAs. After 7 days, the greater number of miRNAs was modulated by fluoxetine (35 miRNAs, mainly up-regulated), while desipramine and agomelatine modulated the expression of 13 and 22 miRNAs, respectively. Finally, 21 days of agomelatine treatment modulated the expression of 6 miRNAs. Interestingly, some of the miRNAs were found to be similarly affected by at least two of the different ADs. A bio-informatic analysis allowed the identification of putative miRNA targets and signalling pathways modulated by the identified miRNAs. The predicted target genes of miRNAs are involved in several pathways related to neuronal functions and ADs mechanism of action; moreover, many of the putative target genes, in particular those of miRs modulated by agomelatine, are enriched in pathways related to DNA/RNA regulation and epigenetic mechanisms. A number of putative miRNA target genes have been selected for validation studies by means of mRNA/protein expression analyses. The results of these work, showing that AD treatments induce early and time-dependent modifications in the expression of hippocampal miRNAs, could be of help to better clarify the ADs mechanism of action and to identify new putative targets for the development of novel drugs with greater efficacy and a more rapid onset of action.
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SGNMRA85M63A246H-Table S4 ENRICHED AGO 07 Chapter 2.pdfTable S4 ENRICHED AGO 07 Chapter 21,99 MBAdobe PDFView/Open
SGNMRA85M63A246H-Table S3 Chapter 2.pdfTable S3 Chapter 2193,26 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S4 OVEREXP AGO 21 Chapter 2.pdfTable S4 OVEREXP AGO 21 Chapter 2307,71 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S4 OVEREXP AGO 07 Chapter 2.pdfTable S4 OVEREXP AGO 07 Chapter 2474,89 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S4 OVEREXP AGO 03-07 Chapter 2.pdfTable S4 OVEREXP AGO 03-07 Chapter 2456,6 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S4 OVEREXP AGO 03 Chapter 2.pdfTable S4 OVEREXP AGO 03 Chapter 2419,29 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S4 ENRICHED GENES AGO 21 Chapter 2.pdfTable S4 ENRICHED GENES AGO 21 Chapter 2579,18 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S4 ENRICHED GENES AGO 03 Chapter 2.pdfTable S4 ENRICHED GENES AGO 03 Chapter 23,85 MBAdobe PDFView/Open
SGNMRA85M63A246H-Table S4 ENRICHED AGO 03-07 Chapter 2.pdfTable S4 ENRICHED AGO 03-07 Chapter 2632,42 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S3 Chapter 2.pdfTable S3 Chapter 2193,26 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S2 Chapter 2.pdfTable S2 Chapter 2375,44 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S1 gene AGO 21 Chapter 2.pdfTable S1 gene AGO 21 Chapter 2314,66 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S1 gene AGO 07 Chapter 2.pdfTable S1 gene AGO 07 Chapter 2637,64 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S1 gene AGO 03 Chapter 2.pdfTable S1 gene AGO 03 Chapter 2916,26 kBAdobe PDFView/Open
SGNMRA85M63A246H-Figure S4 Chapter 2.pdfFigure S4 Chapter 2240,17 kBAdobe PDFView/Open
SGNMRA85M63A246H-Figure S3 Chapter 2.pdfFigure S3 Chapter 2264,95 kBAdobe PDFView/Open
SGNMRA85M63A246H-Figure S2 Chapter 2.pdfFigure S2 Chapter 2272,95 kBAdobe PDFView/Open
SGNMRA85M63A246H-Figure S1 Chapter 2.pdfFigure S1- Chapter2277,72 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S5 OVEREXP FLX 07 Chapter 1.pdfTable S5 OVEREXP FLX 07 Chapter 1348,65 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S5 OVEREXP FLX 03 Chapter 1.pdfTable S5 OVEREXP FLX 03 Chapter 1384,98 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S5 OVEREXP DMI 07 Chapter 1.pdfTable S5 OVEREXP DMI 07 Chapter 1528,26 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S5 OVEREXP DMI 03 Chapter 1.pdfTable S5 OVEREXP DMI 03 Chapter 1370,91 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S5 OVEREXP COMMON DMI-FLX 07 Chapter 1.pdfTable S5 OVEREXP COMMON DMI-FLX 07 Chapter 1381,74 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S5 ENRICHED FLX 07 Chapter 1.pdfTable S5 ENRICHED FLX 07 Chapter 14,05 MBAdobe PDFView/Open
SGNMRA85M63A246H-Table S5 ENRICHED FLX 03 Chapter 1.pdfTable S5 ENRICHED FLX 03 Chapter 1782,6 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S5 ENRICHED DMI 07 Chapter 1.pdfTable S5 ENRICHED DMI 07 Chapter 11,94 MBAdobe PDFView/Open
SGNMRA85M63A246H-Table S5 ENRICHED DMI 03 Chapter 1.pdfTable S5 ENRICHED DMI 03 Chapter 1856,72 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S5 ENRICHED COMMON DMI-FLX 07 Chapter 1.pdfTable S5 ENRICHED COMMON DMI-FLX 07 Chapter 1870,59 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S4 FLX 07 Chapter 1.pdfTable S4 FLX 07 Chapter 1492,62 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S4 FLX 03 Chapter 1.pdfTable S4 FLX 03 Chapter 1197,73 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S4 DMI 07 Chapter 1.pdfTable S4 DMI 07 Chapter 1201,86 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S4 DMI 03 Chapter 1.pdfTable S4 DMI 03 Chapter 1199,18 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S3 targets FLX 07 Chapter 1.pdfTable S3 targets FLX 07 Chapter 12,82 MBAdobe PDFView/Open
SGNMRA85M63A246H-Table S3 targets FLX 03 Chapter 1.pdfTable S3 targets FLX 03 Chapter 1803,71 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S3 targets DMI 07 Chapter 1.pdfTable S3 targets DMI 07 Chapter 11,14 MBAdobe PDFView/Open
SGNMRA85M63A246H-Table S3 targets DMI 03 Chapter 1.pdfTable S3 targets DMI 03 Chapter 1676,46 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S2 Chapter 1.pdfTable S2 Chapter 1354 kBAdobe PDFView/Open
SGNMRA85M63A246H-Table S1 Chapter 1.pdfTable S1 Chapter 1312,6 kBAdobe PDFView/Open
SGNMRA85M63A246H-Figure S3- Chapter 1.pdfFigure S3- Chapter 1187,48 kBAdobe PDFView/Open
SGNMRA85M63A246H-Figure S2- Chapter 1.pdfFigure S2- Chapter 1229,27 kBAdobe PDFView/Open
SGNMRA85M63A246H-Figure S1- Chapter1.pdfFigure S1- Chapter1270,65 kBAdobe PDFView/Open
SGNMRA85M63A246H-tesi dottorato.pdfPhD thesis Mara Seguini2,51 MBAdobe PDFView/Open


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