Is PTSD-Phenotype Associated with HPA-Axis Sensitivity? Feedback Inhibition and Other Modulating Factors of Glucocorticoid Signaling Dynamics
Abstract
:1. Introduction
2. Results
2.1. Behavioral Responses at Day 7 Post-PSS Exposure
2.2. Methylprednisolone Suppression Test (MPST)
2.3. Pulsatile Activity during MPST
2.4. Brain Immunohistochemistry
2.5. Brain GR-ir Cells 8 Days Post-PSS Exposure
2.6. Brain MR-ir Cells 8 Days Post-PSS Exposure
2.7. Brain FKBP5 Levels 8 Days Post-PSS Exposure
2.8. Brain AVP Levels 8 Days Post-PSS Exposure
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. Experimental Design
4.3. Predator Scent Stress (PSS)
4.4. Behavioral Measurements
4.5. Cut-Off Behavioral Criteria (CBC) Model
4.6. Mesh Barrier Housing
4.7. Jugular Vein Catheter Surgery and Blood Sampling
4.8. Measurement of Serum Corticosterone
4.9. Methylprednisolone Suppression Test
4.10. Immunohistochemistry
4.11. Quantification of MR and GR Translocation Patterns in Hippocampal Subregions
4.12. Statistical Analyses
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ANOVA | Analysis of variance |
ASR | Acoustic startle response |
AVP | Arginine vasopressin |
DG | Dentate gyrus |
EBR | Extreme behavioral response |
EPM | Elevated plus-maze |
FKBP5 | FK506-binding protein 51 |
GC | Glucocorticoid |
GR | Glucocorticoid receptor |
HPA | Hypothalamus–pituitary–adrenal |
MBR | Minimal behavioral response |
MPST | Methylprednisolone suppression test |
MR | Mineralocorticoid receptor |
PBR | Partial behavioral response |
PSS | Predator scent stress |
PTSD | Posttraumatic stress disorder |
PVN | Paraventricular nucleus of the hypothalamus |
RM | Repeated measure |
SCN | Suprachiasmatic nucleus |
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Time Post Methylprednisolone Administration | EBR n = 4 | PBR n = 9 | MBR n = 8 | Statistics |
---|---|---|---|---|
20 min | ||||
0–50% Suppression, (n) | 0 | 100%, (9/9) | 87.5%, (7/8) | Pearson χ2 = 12.35, df = 2, p < 0.0025 |
51–89% Suppression, (n) | 100%, (4/4) | 0 | 12.5%, (1/8) | |
90%+ Suppression, (n) | 0 | 0 | 0 | |
40 min | ||||
0–50% Suppression, (n) | 0 | 22%, (2/9) | 75%, (6/8) | Pearson χ2 = 11.23, df = 4, p < 0.025 |
51–89% Suppression, (n) | 25%, (1/4) | 67%, (6/9) | 12.5%, (1/8) | |
90%+ Suppression, (n) | 75%, (3/4) | 11%, (1/9) | 12.5%, (1/8) | |
70 min | ||||
0–50% Suppression, (n) | 0 | 11%, (1/9) | 62.5%, (5/8) | Pearson χ2 = 11.12, df = 4, p < 0.03 |
51–89% Suppression, (n) | 0 | 33%, (3/9) | 25%, (2/8) | |
90%+ Suppression, (n) | 100%, (4/4) | 56%, (5.9) | 12.5%, (1/8) |
Average Pulsatility during MPST | EBR n = 4 (I) | PBR n = 9 (II) | MBR n = 8 (III) | Statistics |
---|---|---|---|---|
Amplitudes average suppression 1 | 0.16 ± 0.1 | 0.036 ± 0.02 | 0 | I ≠ III (Bonferroni) I ≠ II, III (Fisher LSD) |
Amplitudes average recovery 2 | 0.64 ± 0.15 | 0.53 ± 0.13 | 0.24 ± 0.09 | NS |
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Danan, D.; Todder, D.; Zohar, J.; Cohen, H. Is PTSD-Phenotype Associated with HPA-Axis Sensitivity? Feedback Inhibition and Other Modulating Factors of Glucocorticoid Signaling Dynamics. Int. J. Mol. Sci. 2021, 22, 6050. https://doi.org/10.3390/ijms22116050
Danan D, Todder D, Zohar J, Cohen H. Is PTSD-Phenotype Associated with HPA-Axis Sensitivity? Feedback Inhibition and Other Modulating Factors of Glucocorticoid Signaling Dynamics. International Journal of Molecular Sciences. 2021; 22(11):6050. https://doi.org/10.3390/ijms22116050
Chicago/Turabian StyleDanan, Dor, Doron Todder, Joseph Zohar, and Hagit Cohen. 2021. "Is PTSD-Phenotype Associated with HPA-Axis Sensitivity? Feedback Inhibition and Other Modulating Factors of Glucocorticoid Signaling Dynamics" International Journal of Molecular Sciences 22, no. 11: 6050. https://doi.org/10.3390/ijms22116050