Voluntary Exercise Impacts on the Rat Hypothalamic-Pituitary-Adrenocortical Axis Mainly at the Adrenal Level

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Voluntary Exercise Impacts on the Rat
Hypothalamic-Pituitary-Adrenocortical Axis Mainly
at the Adrenal Level

• Susanna K. Droste et. al.

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Previous Work

• Effects of Long-Term Voluntary Exercise on the
  Mouse Hypothalamic-Pituitary-Adrenocortical Axis.
  Droste et. al. (Russ did last week)
• Mice showed benefits from long-term Ve
• Modified glucocorticoid responses to stressful
  events (incr. to physiological decr. to psych)
• Resulting from alterations in SAM control of
  glucocorticoid secretion, at least in the mouse.

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Current Study

• Aims to determine effects of long-term Ve on rat
  HPA axis under baseline conditions and response
  to physiological and psychological stressors
• Show Ve exerts effects at adrenal gland level
  possibly involving changes in SAM input.

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Big Picture!

• Hallmarks of mood disorders
• Impaired negative feedback in the HPA axis SNS
• hypersecretion of glucocorticoid hormones
  (cortisol/corticosterone)

• If same results are seen in rats, these effects
  could be phylogenetically conserved (maybe in
  primates)
• Important for examining health and disease

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Animals Used

• Male Sprague-Dawley rats (140-160g)
• Singly housed under standard lighting, humidity,
  temp.
• Light Cycle (??) always say in methods!!
• Food and H2O available ad libitum

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Voluntary EXERCISE Paradigm

• 5 day habituation to wheel
• Ve group allowed free access to running wheel in
  home cage for 4 weeks
• Ran 4-7km per night

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Physical Parameters

• Measured weight, food and water

• Note significant differences

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Physical Parameters Cont

• After experiment removed and weighed
• abdominal adipose tissue (Ve )
• Thymus (Ve )
• pituitary gland (Ve NC)
• adrenal glands (Ve )
• Indicates elevated activity of HPA axis

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Physical Parameter Changes
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Adrenal Glands

• Bi-Lateral structure sits on each kidney like a
  hat
• Separated into two regions Cortex and Medulla
• Cortex produces glucocorticoids (B)
• Medulla produces catecholamines and
• endogenous opiates
• Note Borrowed w/o permission from Russ Carpenter!

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Changes in Adrenal Gland
MICE ONLY IN RIGHT
NO ADRENAL ASYMMETRY
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Neuroendocrine Experiments

• Conducted after 4 wks of Ve
• All exp performed between 7am to 11am
  (Dark/Light??)
• This ensures baseline plasma ACTH and
  corticosterone levels
• Animals anesthetized and trunk blood collected

• To determine stress response, rats exposed to
• A novel environment- a clean cage for 30 minutes
• 15 min forced swim
• Tested ACTH and B
• Whats the difference between the two?

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Enhanced B release
Blunted B release
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Behavior in Novel Environment
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Exploring changes in corticosteroid receptor
expression involved in HPA axis
Learning and Memory
Anxiety/ HPA feedback
Cognition/Anxiety/HPA feedback
HPA regulation
HPA regulation
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CRH, AVP and OXY mRNA expression in PVN
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SCN
AVP
OXY
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Discussion

• Both macroscopic and functional changes point to
  adrenal gland as part of HPA axis where exercise
  effects converge
• Mice showed increase only in right adrenal cortex
  vs. rats showed increase in both adrenal cortices
• Species specific or other mechanisms in
  conjunction with SAM input?

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Ve verses Forced exercise

• Run or be Shocked!

• Other research observed enlarged adrenal medullas
  with use of forced exercise (Fe)
• Ve paradigm is not comparable to Fe because Fe
  changes go beyond changes in Ve mice and rats
• Fe produces SEVERE stress like changes in HPA
  axis
• The type of exercise matters!

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Novel cage exposure a psychological stress

• Ve rats relaxed during last 15 min (of 30) in
  novel cage decreased emotionality
• Dovetails with in GR which down regulates
  HPA axis
• Ve rats turn-off HPA (at adrenals) better than
  control rats

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Forced swimming- a physiological stress

• ACTH unchanged for Ve vs control
• Enhanced cort response in Ve
• Could be adaptive for physical activity
  requirements
• Mediated through SNS?

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Exercise does

• Increases GR/MR in the hippocampus (1)
• Modifies SAM activity (2)
• Does not change hypothalamic activity (3)
• Does not change pituitary release (4)
• Modifies adrenal structure (5)
• Modifies cort response to stress (phys and psych)
  (6)

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1
3
6
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SNS
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Adrenal Medulla
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The End