Transcript Effects of spontaneous and forced running on activation of

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 CRHcontaining 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
ByeBye!