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 H 2 O

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 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 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

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