Adverse maternal environment and western diet impairs cognitive function and alters hippocampal glucocorticoid receptor promoter methylation in male mice
| Autor: | Amber Majnik, Jennifer Sterrett, Robert H. Lane, Cecilia J. Hillard, Xingrao Ke, Qi Fu |
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| Rok vydání: | 2019 |
| Předmět: |
Male
medicine.medical_specialty Physiology Offspring hippocampus Hippocampus 030204 cardiovascular system & hematology Biology Hippocampal formation adverse maternal environment lcsh:Physiology Fetal Development 03 medical and health sciences Exon Mice Random Allocation 0302 clinical medicine Glucocorticoid receptor Receptors Glucocorticoid Downregulation and upregulation Pregnancy Physiology (medical) Internal medicine medicine Transcriptional regulation Animals Cognitive Dysfunction Promoter Regions Genetic Maternal-Fetal Exchange Original Research DNA methylation lcsh:QP1-981 western diet Mice Inbred C57BL GR Endocrinology Diet Western Maternal Exposure Prenatal Exposure Delayed Effects Female 030217 neurology & neurosurgery |
| Zdroj: | Physiological Reports Physiological Reports, Vol 8, Iss 8, Pp n/a-n/a (2020) |
| ISSN: | 2051-817X |
| Popis: | Adverse maternal environment (AME) and high‐fat diet in early childhood increase the risk of cognitive impairment and depression later in life. Cognitive impairment associates with hippocampal dysfunction. A key regulator of hippocampal function is the glucocorticoid receptor. Increased hippocampal GR expression associates with cognitive impairment and depression. Transcriptional control of GR relies in part upon the DNA methylation status at multiple alternative initiation sites that are tissue specific, with exon 1.7 being hippocampal specific. Increased exon 1.7 expression associates with upregulated hippocampal GR expression in early life stress animal models. However, the effects of AME combined with postweaning western diet (WD) on offspring behaviors and the expression of GR exon 1 variants in the hippocampus are unknown. We hypothesized that AME and postweaning WD would impair cognitive function and cause depression‐like behavior in offspring in conjunction with dysregulated hippocampal expression of total GR and exon 1.7 variant in mice. We found that AME‐WD impaired learning and memory in male adult offspring concurrently with increased hippocampal expression of total GR and GR 1.7. We also found that increased GR 1.7 expression was associated with decreased DNA methylation at the GR 1.7 promoter. We speculate that decreased DNA methylation at the GR 1.7 promoter plays a role in AME‐WD induced increase of GR in the hippocampus. This increased GR expression may subsequently contribute to hippocampus dysfunction and lead to the cognitive impairment seen in this model. The central findings of this study are that AME and WD together decrease learning and memory in male adult offspring. This impaired learning and memory was concurrent with changes in hippocampal GR1.7 expression, DNA methylation, and GR signaling relative to AME or postweaning WD alone. This combination is relevant considering the previous literature associating neurocognitive impairment and hippocampal GR biology. |
| Databáze: | OpenAIRE |
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