Exposure to Early Life Stress Results in Epigenetic Changes in Neurotrophic Factor Gene Expression in a Parkinsonian Rat Model
Early life adversity increases the risk of mental disorders later in life. Chronic early life stress may alter neurotrophic factor gene expression including those for brain derived neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF) that are important in neuronal growth, sur...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Parkinson's Disease |
| Online Access: | http://dx.doi.org/10.1155/2016/6438783 |
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| author | Thabisile Mpofana Willie M. U. Daniels Musa V. Mabandla |
| author_facet | Thabisile Mpofana Willie M. U. Daniels Musa V. Mabandla |
| author_sort | Thabisile Mpofana |
| collection | DOAJ |
| description | Early life adversity increases the risk of mental disorders later in life. Chronic early life stress may alter neurotrophic factor gene expression including those for brain derived neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF) that are important in neuronal growth, survival, and maintenance. Maternal separation was used in this study to model early life stress. Following unilateral injection of a mild dose of 6-hydroxydopamine (6-OHDA), we measured corticosterone (CORT) in the blood and striatum of stressed and nonstressed rats; we also measured DNA methylation and BDNF and GDNF gene expression in the striatum using real time PCR. In the presence of stress, we found that there was increased corticosterone concentration in both blood and striatal tissue. Further to this, we found higher DNA methylation and decreased neurotrophic factor gene expression. 6-OHDA lesion increased neurotrophic factor gene expression in both stressed and nonstressed rats but this increase was higher in the nonstressed rats. Our results suggest that exposure to early postnatal stress increases corticosterone concentration which leads to increased DNA methylation. This effect results in decreased BDNF and GDNF gene expression in the striatum leading to decreased protection against subsequent insults later in life. |
| format | Article |
| id | doaj-art-463bfd418d6244f99b88b97985a7d102 |
| institution | Kabale University |
| issn | 2090-8083 2042-0080 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Parkinson's Disease |
| spelling | doaj-art-463bfd418d6244f99b88b97985a7d1022025-02-03T01:07:48ZengWileyParkinson's Disease2090-80832042-00802016-01-01201610.1155/2016/64387836438783Exposure to Early Life Stress Results in Epigenetic Changes in Neurotrophic Factor Gene Expression in a Parkinsonian Rat ModelThabisile Mpofana0Willie M. U. Daniels1Musa V. Mabandla2Discipline of Human Physiology, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South AfricaDiscipline of Human Physiology, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South AfricaDiscipline of Human Physiology, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South AfricaEarly life adversity increases the risk of mental disorders later in life. Chronic early life stress may alter neurotrophic factor gene expression including those for brain derived neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF) that are important in neuronal growth, survival, and maintenance. Maternal separation was used in this study to model early life stress. Following unilateral injection of a mild dose of 6-hydroxydopamine (6-OHDA), we measured corticosterone (CORT) in the blood and striatum of stressed and nonstressed rats; we also measured DNA methylation and BDNF and GDNF gene expression in the striatum using real time PCR. In the presence of stress, we found that there was increased corticosterone concentration in both blood and striatal tissue. Further to this, we found higher DNA methylation and decreased neurotrophic factor gene expression. 6-OHDA lesion increased neurotrophic factor gene expression in both stressed and nonstressed rats but this increase was higher in the nonstressed rats. Our results suggest that exposure to early postnatal stress increases corticosterone concentration which leads to increased DNA methylation. This effect results in decreased BDNF and GDNF gene expression in the striatum leading to decreased protection against subsequent insults later in life.http://dx.doi.org/10.1155/2016/6438783 |
| spellingShingle | Thabisile Mpofana Willie M. U. Daniels Musa V. Mabandla Exposure to Early Life Stress Results in Epigenetic Changes in Neurotrophic Factor Gene Expression in a Parkinsonian Rat Model Parkinson's Disease |
| title | Exposure to Early Life Stress Results in Epigenetic Changes in Neurotrophic Factor Gene Expression in a Parkinsonian Rat Model |
| title_full | Exposure to Early Life Stress Results in Epigenetic Changes in Neurotrophic Factor Gene Expression in a Parkinsonian Rat Model |
| title_fullStr | Exposure to Early Life Stress Results in Epigenetic Changes in Neurotrophic Factor Gene Expression in a Parkinsonian Rat Model |
| title_full_unstemmed | Exposure to Early Life Stress Results in Epigenetic Changes in Neurotrophic Factor Gene Expression in a Parkinsonian Rat Model |
| title_short | Exposure to Early Life Stress Results in Epigenetic Changes in Neurotrophic Factor Gene Expression in a Parkinsonian Rat Model |
| title_sort | exposure to early life stress results in epigenetic changes in neurotrophic factor gene expression in a parkinsonian rat model |
| url | http://dx.doi.org/10.1155/2016/6438783 |
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