Effects of spontaneous and forced running on activation of hypothalamic corticotropin- releasing hormone neurons in rats
Jan 06, 2018
Effects of spontaneous and forced running on activation
of hypothalamic corticotropin-releasing
hormone neurons in rats
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
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
HPA axis
Introduction
Forced physical exercise (running/swimming) produces negative adaptations to stress responses with activation of CRH neurons
Therefore, physical exercise could alter psychological effects
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
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
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
Figure 1
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
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
Figure 2
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
M & M
Quantitative analysis performed on all PVN coronal sections
c-Fos & CRH counted on PVN sections
c-Fos counted in the LC sections
Figure 3
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
Figure 4
Discussion
Forced physical exercise = strong stressor
Previously, forced swimming strongly induces CRH mRNA in PVN
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
Figure 1
Figure 2
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)
Discussion
Chronic HPA axis stimulation produces negative physiological adaptations such as depression and anxiety
Spontaneous exercise training could improve stress response
SWR = mild stressor
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
Discussion
Acute exercise effects on CRH activation definitely depends on modality rather than intensity
Bye-Bye!