Ansing, G. (Gerdi) (2019) FKBP5 risk gene does not alter peripartum-associated changes in hypothalamic gene expression. thesis, Medicine.
Full text available on request.Abstract
Aim: The pathophysiology of peripartum depression is unknown. However, there are different theories described, included changes in the HPA axis, epigenetic influences and hormonal changes. FKBP5 is a risk gene for unipolar depression and PTSD and gives hyperactivity of the HPA axis. The aim of this study was to asses if FKBP5 changes the normal hormonal alterations during pregnancy and postpartum. To elucidate the effect of the humanized FKBP5 genotype on the hypothalamic expression of AVP, Prolactin and GR in mice in the peripartum period, the understanding about the influence of the FKBP5 gene on peripartum depression will be increased. Methods: C57BL/6 mice with humanized FKBP5 risk (rs1360780-T) allele, C5BL/6 mice with the FKBP5 resiliency (rs1360780-C) allele, C57BL/6 Wild Type, Mixed Swiss Webster Wild Type and Mixed Swiss Webster Knock Out mice were killed during pregnancy and 2 day postpartum. qPCR of the hypothalami of the different mice group was performed to measure the mRNA expression levels of AVP, Prolactin and GR. Results: No significant differences between the expression levels of the FKBP5 risk (rs1360780-T) group and the other groups was found. The mean expression levels of AVP and Prolactin in the hypothalamus from the C57BL/6 mice were significant higher postpartum than during pregnancy. The mean hypothalamic expression level of GR in the C57BL/6 mice was significant lower postpartum than during pregnancy. Interpretation: In line with the literature, hypothalamic AVP and Prolactin mRNA levels are higher postpartum than during pregnancy of mice. A novel finding is that GR expression is decreased in postpartum mice compared with pregnant mice. The major outcome of this study is that the genotype FKBP5 did not influence the hypothalamic expression of AVP, Prolactin or GR in the peripartum period. Because this is the first research with humanized FKBP5 mice, the study should be optimized and repeated to investigate the influence of FKBP5 on peripartum depression.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | FACULTY SUPERVISOR: and Walrave, dr. T.R.W.M. and Ziekenhuisgroep Twente Psychiatry, Mother-Baby-Unit |
| Supervisor name: | SUPERVISOR: and Slattery, Prof. Dr. D.A. and Goethe University Hospital, Group of Translation Psychiatry |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:44 |
| Last Modified: | 25 Jun 2020 10:44 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/576 |
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