Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing...
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![Page 1: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/1.jpg)
Effects of spontaneous and forced running on activation
of hypothalamic corticotropin-releasing
hormone neurons in rats
![Page 2: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/2.jpg)
Introduction
Stressors such as immobilization, restraint, foot shock, & communication box activate CRH-containing neurons in the PVN
Acute physical stress – treadmill running – induces strong CRH mRNA expression in the PVN
![Page 3: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/3.jpg)
Introduction
Physical exercise = stressor Physical exercise triggers the HPA
axis starting with the CRH neurons CRH neurons project to brain areas
involved in mood/affect
![Page 4: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/4.jpg)
HPA axis
![Page 5: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/5.jpg)
Introduction
Forced physical exercise (running/swimming) produces negative adaptations to stress responses with activation of CRH neurons
Therefore, physical exercise could alter psychological effects
![Page 6: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/6.jpg)
Introduction
Spontaneous physical exercise could be beneficial to all aspects of health, so…
Effects of CRH neuron activation by physical exercise should differ between spontaneous & forced
![Page 7: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/7.jpg)
Purpose of the Study
Compare hypothalamic CRH neuronal activation during spontaneous wheel runners (SWR) & forced wheel runners (FWR) with double-staining for c-Fos and CRH in the PVN
![Page 8: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/8.jpg)
Materials & Methods
Twenty adult male Wistar rats Individual housed cages attached to
voluntarily accessible running wheels unlocked in all cages for habituation 1 week before testing
12h light/dark cycle Ad libitum access to food and H2O
![Page 9: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/9.jpg)
Figure 1
![Page 10: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/10.jpg)
M & M
FWR distance = SWR distance 1 hr spontaneous or forced wheel
running in the dark cycle FWR were “softly” prodded when
they stopped running Control rats were left in locked
wheels for 1 hr without wheel running or prodded 25-30 times
![Page 11: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/11.jpg)
M & M
30 mins after running, rats were put to sleep by injection and perfused by heparin, other stuff, and PBS
Brains frozen, cut on coronal plane, and collected in PBS + Na+ azide
Antibodies were used to visualize c-Fos & CRH
![Page 12: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/12.jpg)
Figure 2
![Page 13: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/13.jpg)
M & M
Anti-CRH antibody reacts only with CRH peptide
c-Fos localized to cell nuclei and appeared as a dark gray-black stain
CRH localized to cell cytoplasm and appeared as light-brown staining
![Page 14: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/14.jpg)
M & M
Quantitative analysis performed on all PVN coronal sections
c-Fos & CRH counted on PVN sections
c-Fos counted in the LC sections
![Page 15: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/15.jpg)
Figure 3
![Page 16: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/16.jpg)
Results
Double Fos/CRH-positive cells ↑FWR, ↓SWR & controls
Increase of FWR was extremely significant Prodding alone did not increase
c-Fos/CRH cells significantly Both FWR & SWR enhanced Fos
expression in the LC compared to controls
![Page 17: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/17.jpg)
Figure 4
![Page 18: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/18.jpg)
Discussion
Forced physical exercise = strong stressor
Previously, forced swimming strongly induces CRH mRNA in PVN
![Page 19: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/19.jpg)
Forced Swim Stress
↑CRH hnRNA after 10 min swim stress and then returned to baseline
AVP hnRNA in PVN (colocalization w/CRH) remained relatively the same @ 10min
Significantly ↑AVP 2h after stress Pre-Tx w/dexamethasone → no
CRH/AVP increase after stress
![Page 20: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/20.jpg)
Figure 1
![Page 21: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/21.jpg)
Figure 2
![Page 22: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/22.jpg)
Discussion
Synergistic effects of FWR + prodding likely comprised the significant rise in Fos/CRH-positive neurons
Previously, several negative adaptations were revealed during treadmill running (equivalent to FWR)
![Page 23: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/23.jpg)
Discussion
Chronic HPA axis stimulation produces negative physiological adaptations such as depression and anxiety
Spontaneous exercise training could improve stress response
SWR = mild stressor
![Page 24: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/24.jpg)
Discussion
FWR & SWR enhanced Fos in LC which conflicts with CRH neuronal effects in the PVN
Both FWR & SWR ↑NE levels Acute stress ↑effects on LC & PVN
neurons → ↑Fos This study showed CRH activation
might depend on exercise type
![Page 25: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/25.jpg)
Discussion
Acute exercise effects on CRH activation definitely depends on modality rather than intensity
![Page 26: Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats.](https://reader033.fdocuments.us/reader033/viewer/2022050812/5a4d1adb7f8b9ab059974e0f/html5/thumbnails/26.jpg)
Bye-Bye!