1 / 25

S. K. Droste , M. C. Schweizer , S. Ulbrich , and J. M. H. M. Reul

Long-Term Voluntary Exercise and the Mouse Hypothalamic-Pituitary- Adrenocorticoid Axis: Impact of Concurrent Treatment with the Antidepressant Drug Tianeptine. S. K. Droste , M. C. Schweizer , S. Ulbrich , and J. M. H. M. Reul Journal of Neuroendocrinology Volume 18, pages 915-925 2006.

Télécharger la présentation

S. K. Droste , M. C. Schweizer , S. Ulbrich , and J. M. H. M. Reul

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.


Presentation Transcript

  1. Long-Term Voluntary Exercise and the Mouse Hypothalamic-Pituitary-Adrenocorticoid Axis: Impact of Concurrent Treatment with the Antidepressant Drug Tianeptine S. K. Droste, M. C. Schweizer, S. Ulbrich, and J. M. H. M. Reul Journal of Neuroendocrinology Volume 18, pages 915-925 2006

  2. Known effects of exercise • Positive effects on the brain • Decreases depression and anxiety • increased neurogenesis in Hc • Increased growth factors (IGF-1, BDNF) • Role of glutamate • Changes in the HPA axis • Decreased HPA sensitivity • Increased stress coping • Improved sleep quality

  3. Known Effects of Antidepressants • Increased neurogenesis in the dentate gyrus • Role of glutamate • Affects the HPA axis similar to exercise • decreased stress response • decrease in anxiety-related behavior • Improved sleep quality • Normalization of the HPA axis function

  4. Synergistic effects of exercise and antidepressant drug • BDNF expression in the hippocampus • Many overlapping effects • Suggested beneficial effects of exercise on the clinical course of antidepressant-treated patients

  5. Aim of study - To investigate whether voluntary exercise and antidepressant co-treatment exert synergistic effects on the mouse HPA axis

  6. Animals • Male C57BL/6N mice • 10-12 weeks in age • Singly housed • 12:12 h light/dark cycle • Lights on 6.00 h

  7. Drug Treatment • Antidepressent – Tianeptine • Shown to regulate neuroplasticity • Stimulate uptake of serotonin in cortex and hippocampus • Same effects on depression treatment as: • TCA (tricyclic antidepressant) and • SSRI’s (selective serotonin reuptake inhibitors)

  8. Dosage & Method of Administration • 20 mg/kg body weight per day • Administered in drinking water • Prevent a non specific stress effect in response to a series of injections • Dark water bottles • prevent the light sensitive tianeptine from breaking down

  9. Dosage & Method of Administration • Collected liquid intake over a 24 hour period (done twice a week) • Calculated a mean liquid intake for each week and mouse (ml/day) • [tianeptine] in drinking water adjusted throughout experiment • Compensate for changes in weight and liquid intake • The control group of mice got tap water

  10. Groups • Sedentary (S) • Exercise (E) • Antidepressant (A) • Exercise + Antidepressant (E+A)

  11. Voluntary exercise paradigm • Habituation to the housing conditions- 5 days • “E” and “E + A” had free access to running wheel in their home cages for 4 weeks • At this time antidepressant treatment began • Mice ran mainly during the first half of the dark phase of the diurnal cycle • Housing conditions of “A” and “S” remained unchanged

  12. Assessment of physical measures • Weighed weekly • Only tissues of mice killed under baseline conditions (7-9am) were collected for physical and gene expression measures • Tissues collected included: • Brain, Adipose, Thymus, Adrenal

  13. Following experimental period: • Exposed to a novel environment, or • Placed in a single clean cage with new sawdust and no food and water for 30 minutes • Extra variable: half control and exercise mice were provided with a clean running wheel in the new cage • Check for impact of novel environment on different groups • Restraint stress procedure. • Placed in a clear plastic tube for 30 minutes • Hormones assessed from trunk blood

  14. Killing process • Anaesthetized in a glass jar • Isoflurane vapour • Decapitated immediately following anesthesia exposure • Trunk blood collected

  15. Wheel running – Figure 1

  16. Liquid Intake – figure 2

  17. Weight – figure 3 Body Weight Abdominal Fat

  18. Adrenal Glands - figure 4 Left + Right Adrenal Left Adrenal Right Adrenal

  19. TH mRNA expression in adrenal medulla and locus coeruleus– figure 5 Adrenal Medulla Locus coeruleus

  20. ACTH Corticosterone Baseline and Stress-induced plasma ACTH and corticosterone levels - figure 6

  21. E and E+A decrease baseline levels of corticosterone • E and E+A decrease corticosterone response to novel environment • BUT… E and E+A increase corticosterone response to restraint stress • Figure 6 • CRH is decreased with exercise • Would expect to see a decrease in ACTH • But you don’t, ACTH is unaffected • Figures 6 & 7

  22. CRF mRNA expression in hypothalamic PVN – figure 7

  23. Conclusion • Concurrent long-term voluntary exercise and tianeptine treatment exert a potent action on the mouse HPA axis • Strongest impact on the adrenal gland • Synergistic action affecting adrenal structure and function • Mechanisms at the adrenal level are key in modulating glucocorticoidsecretory output • Complex interactions of exercise, tianeptine, and stress coping

  24. The EndHave a Great Christmas Break!

More Related