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Norepinephrine and Glucocorticoids Modulate Chronic Unpredictable Stress-Induced Increase in the Type 2 CRF and Glucocorticoid Receptors in Brain Structures Related to the HPA Axis Activation.
- Source :
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Molecular neurobiology [Mol Neurobiol] 2021 Oct; Vol. 58 (10), pp. 4871-4885. Date of Electronic Publication: 2021 Jul 02. - Publication Year :
- 2021
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Abstract
- The stress response is multifactorial and enrolls circuitries to build a coordinated reaction, leading to behavioral, endocrine, and autonomic changes. These changes are mainly related to the hypothalamus-pituitary-adrenal (HPA) axis activation and the organism's integrity. However, when self-regulation is ineffective, stress becomes harmful and predisposes the organism to pathologies. The chronic unpredictable stress (CUS) is a widely used experimental model since it induces physiological and behavioral changes and better mimics the stressors variability encountered in daily life. Corticotropin-releasing factor (CRF) and glucocorticoids (GCs) are deeply implicated in the CUS-induced physiological and behavioral changes. Nonetheless, the CUS modulation of CRF receptors and GR and the norepinephrine role in extra-hypothalamic brain areas were not well explored. Here, we show that 14 days of CUS induced a long-lasting HPA axis hyperactivity evidenced by plasmatic corticosterone increase and adrenal gland hypertrophy, which was dependent on both GCs and NE release induced by each stress session. CUS also increased CRF <subscript>2</subscript> mRNA expression and GR protein levels in fundamental brain structures related to HPA regulation and behavior, such as the lateral septal nucleus intermedia part (LSI), ventromedial hypothalamic nucleus (VMH), and central nucleus of the amygdala (CeA). We also showed that NE participates in the CUS-induced increase in CRF <subscript>2</subscript> and GR levels in the LSI, reinforcing the locus coeruleus (LC) involvement in the HPA axis modulation. Despite the CUS-induced molecular changes in essential areas related to anxiety-like behavior, this phenotype was not observed in CUS animals 24 h after the last stress session.<br /> (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Subjects :
- Animals
Chronic Disease
Glucocorticoids metabolism
Male
Norepinephrine metabolism
Rats
Rats, Wistar
Stress, Psychological psychology
Brain metabolism
Hypothalamo-Hypophyseal System metabolism
Pituitary-Adrenal System metabolism
Receptors, Corticotropin-Releasing Hormone metabolism
Receptors, Glucocorticoid metabolism
Stress, Psychological metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1559-1182
- Volume :
- 58
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Molecular neurobiology
- Publication Type :
- Academic Journal
- Accession number :
- 34213722
- Full Text :
- https://doi.org/10.1007/s12035-021-02470-2