Adverse early life environment induces anxiety-like behavior and increases expression of FKBP5 mRNA splice variants in mouse brain
| Autor: | Xingrao Ke, Qiuli Liu, Amber Majnik, Robert H. Lane, Susan S. Cohen, Qi Fu |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Hypothalamo-Hypophyseal System Physiology Pituitary-Adrenal System Hippocampus Anxiety Biology Bioinformatics Tacrolimus Binding Proteins 03 medical and health sciences Receptors Glucocorticoid 0302 clinical medicine Glucocorticoid receptor Pregnancy Genetics medicine Animals Protein Isoforms splice RNA Messenger Prefrontal cortex Depression (differential diagnoses) Behavior Animal Body Weight Brain Mice Inbred C57BL 030104 developmental biology Animals Newborn Hypothalamus Female Microglia FKBP5 medicine.symptom Corticosterone Stress Psychological 030217 neurology & neurosurgery |
| Zdroj: | Physiological Genomics. 50:973-981 |
| ISSN: | 1531-2267 1094-8341 |
| DOI: | 10.1152/physiolgenomics.00054.2018 |
| Popis: | Adverse early life environment (AELE) predisposes adult offspring toward anxiety disorders. Anxiety disorders are associated with prenatal injuries in key regions of the brain including prefrontal cortex (PFC), hippocampus (HP), and hypothalamus (HT). Injuries in these brain regions result in an impaired hypothalamus-pituitary-adrenal axis (HPA axis) and stress response. An important regulator of the stress response is FK506-binding protein 5 (FKBP5). FKBP5 is a cochaperone of the glucocorticoid receptor (GR) and inhibits GR-mediated regulatory feed-back on the HPA axis in response to stress. Human studies have shown that polymorphisms of FKBP5 are associated with higher FKBP5 levels. Increased FKBP5 leads to GR resistance and impaired negative feedback, which is associated with anxiety disorders. FKBP5 and its mRNA splice variants in the aforementioned brain regions have not been reported. We hypothesized that AELE will increase expression of FKBP5 and its mRNA splice variants in PFC, HP, and HT as well as increase anxiety in adult mice. AELE increased expression of FKBP5 and its mRNA variants in PFC, HP and HT at postnatal day 21. Additionally, AELE caused anxiety and increased GR abundance in association with these changes in FKBP5 expression. We speculate that these changes in FKBP5 mRNA variants affect HPA axis function and contributes to subsequent anxiety-like behavior later in life in AELE mice. |
| Databáze: | OpenAIRE |
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