Alterations of DNA Methylation at GDNF Gene Promoter in the Ventral Tegmental Area of Adult Depression-Like Rats Induced by Maternal Deprivation
Objective: To study the expression and DNA methylation of the Glial cell line-derived neurotrophic factor (GDNF) gene in the development of depression-like behaviors in rats experiencing maternal deprivation stress in early life.Methods: Newborn SD rats were randomly assigned to a normal control gro...
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| Format: | Article |
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Frontiers Media S.A.
2019-01-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fpsyt.2018.00732/full |
| _version_ | 1818514218227335168 |
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| author | Yi Zhang Lei Wang Xin Wang Yuting Wang Yuting Wang Chuting Li Xiongzhao Zhu |
| author_facet | Yi Zhang Lei Wang Xin Wang Yuting Wang Yuting Wang Chuting Li Xiongzhao Zhu |
| author_sort | Yi Zhang |
| collection | DOAJ |
| description | Objective: To study the expression and DNA methylation of the Glial cell line-derived neurotrophic factor (GDNF) gene in the development of depression-like behaviors in rats experiencing maternal deprivation stress in early life.Methods: Newborn SD rats were randomly assigned to a normal control group (NOR) or maternal deprivation group (MD). An open field test (OPT), sucrose preference test (SPT), and a forced swimming test (FST) were used to evaluate rats' behaviors. Protein, mRNA, and methylation levels were measured by ELISA/Western blot, real-time PCR, and BiSulfte Amplicon sequencing PCR, respectively.Results: MD rats had significantly shorter total distance and more fecal pellets in OPT, a lower sucrose preference rate in SPT, and a longer immobility time in FST than NOR rats. Compared with NOR rats, MD rats showed a significantly higher plasma corticosterone (CORT) level. The levels of plasma dopamine (DA) and the GDNF were significantly lower in the MD rats than in NOR rats. In the ventral tegmental area (VTA) tissues, MD rats had a significantly higher level of methylation at the GDNF gene promoter than NOR rats. The expression of the GDNF mRNA and protein were significantly lower in MD rats than in NOR rats. The total distance was significantly correlated with plasma DA and GDNF, the DNA methylation level at the GDNF promoter and the GDNF mRNA level in the VTA. Fecal pellets showed a significant correlation with plasma CORT. The sucrose preference rate was significantly correlated with plasma DA, the DNA methylation level at the GDNF promoter and the GDNF mRNA level in the VTA. Immobility time showed a significant correlation with the plasma DA, the plasma GDNF and the GDNF mRNA level in the VTA.Conclusion: up-regulation of DNA methylation at the GDNF gene promotor and the subsequent down-regulation of the GDNF gene expression in the VTA, may be involved in the development of depression-like behaviors in rats experiencing MD in early life. |
| first_indexed | 2024-12-11T00:12:46Z |
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| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-12-11T00:12:46Z |
| publishDate | 2019-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj.art-91249701e07c40d897584c8ccccf33602022-12-22T01:28:06ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402019-01-01910.3389/fpsyt.2018.00732425198Alterations of DNA Methylation at GDNF Gene Promoter in the Ventral Tegmental Area of Adult Depression-Like Rats Induced by Maternal DeprivationYi Zhang0Lei Wang1Xin Wang2Yuting Wang3Yuting Wang4Chuting Li5Xiongzhao Zhu6Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, ChinaMedical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, ChinaMedical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, ChinaMedical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Clinical Psychology, Maternal and Child Health Hospital of Hunan Province, Changsha, ChinaMedical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, ChinaMedical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, ChinaObjective: To study the expression and DNA methylation of the Glial cell line-derived neurotrophic factor (GDNF) gene in the development of depression-like behaviors in rats experiencing maternal deprivation stress in early life.Methods: Newborn SD rats were randomly assigned to a normal control group (NOR) or maternal deprivation group (MD). An open field test (OPT), sucrose preference test (SPT), and a forced swimming test (FST) were used to evaluate rats' behaviors. Protein, mRNA, and methylation levels were measured by ELISA/Western blot, real-time PCR, and BiSulfte Amplicon sequencing PCR, respectively.Results: MD rats had significantly shorter total distance and more fecal pellets in OPT, a lower sucrose preference rate in SPT, and a longer immobility time in FST than NOR rats. Compared with NOR rats, MD rats showed a significantly higher plasma corticosterone (CORT) level. The levels of plasma dopamine (DA) and the GDNF were significantly lower in the MD rats than in NOR rats. In the ventral tegmental area (VTA) tissues, MD rats had a significantly higher level of methylation at the GDNF gene promoter than NOR rats. The expression of the GDNF mRNA and protein were significantly lower in MD rats than in NOR rats. The total distance was significantly correlated with plasma DA and GDNF, the DNA methylation level at the GDNF promoter and the GDNF mRNA level in the VTA. Fecal pellets showed a significant correlation with plasma CORT. The sucrose preference rate was significantly correlated with plasma DA, the DNA methylation level at the GDNF promoter and the GDNF mRNA level in the VTA. Immobility time showed a significant correlation with the plasma DA, the plasma GDNF and the GDNF mRNA level in the VTA.Conclusion: up-regulation of DNA methylation at the GDNF gene promotor and the subsequent down-regulation of the GDNF gene expression in the VTA, may be involved in the development of depression-like behaviors in rats experiencing MD in early life.https://www.frontiersin.org/article/10.3389/fpsyt.2018.00732/fullmaternal deprivationdepressionGDNFDNA methylationventral regimental area |
| spellingShingle | Yi Zhang Lei Wang Xin Wang Yuting Wang Yuting Wang Chuting Li Xiongzhao Zhu Alterations of DNA Methylation at GDNF Gene Promoter in the Ventral Tegmental Area of Adult Depression-Like Rats Induced by Maternal Deprivation Frontiers in Psychiatry maternal deprivation depression GDNF DNA methylation ventral regimental area |
| title | Alterations of DNA Methylation at GDNF Gene Promoter in the Ventral Tegmental Area of Adult Depression-Like Rats Induced by Maternal Deprivation |
| title_full | Alterations of DNA Methylation at GDNF Gene Promoter in the Ventral Tegmental Area of Adult Depression-Like Rats Induced by Maternal Deprivation |
| title_fullStr | Alterations of DNA Methylation at GDNF Gene Promoter in the Ventral Tegmental Area of Adult Depression-Like Rats Induced by Maternal Deprivation |
| title_full_unstemmed | Alterations of DNA Methylation at GDNF Gene Promoter in the Ventral Tegmental Area of Adult Depression-Like Rats Induced by Maternal Deprivation |
| title_short | Alterations of DNA Methylation at GDNF Gene Promoter in the Ventral Tegmental Area of Adult Depression-Like Rats Induced by Maternal Deprivation |
| title_sort | alterations of dna methylation at gdnf gene promoter in the ventral tegmental area of adult depression like rats induced by maternal deprivation |
| topic | maternal deprivation depression GDNF DNA methylation ventral regimental area |
| url | https://www.frontiersin.org/article/10.3389/fpsyt.2018.00732/full |
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