Transcript The Anteroventral Bed Nucleus of the Strial Terminalis

The Anteroventral BST Differentially
Regulates HPA Axis Responses to
Acute and Chronic Stress
Choi DC, Evanson NK, Furay AR, Ulrich-Lai YM
Ostrander MM, Herman JP.
Introduction
Chronic Stress
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Decreases body weight and food intake
Induces adrenal hypertrophy
Involution of thymus
Affects neuronal plasticity
Elevated expressions of CRH mRNA
Elevated expressions of AVP mRNA
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(in some stress models)
Increased circulating glucocorticoids
The comparison between acute and
chronic stress regarding the HPA axis
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Acute activation of the HPA axis is an
adaptive response
Chronic activation of the HPA axis can be
deleterious and has been linked to several
different pathologies.
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Different brain circuitries are involved in
acute and chronic stress responses.
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Paraventricular thalamus regulate HPA axis
responses to chronic stressors.
Chronic stress can produce enhancement of
HPA axis responses to new stressors.
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Repeated experience with the same (homotypic)
stressor produces habituation of HPA axis
responses.
Repeated homotypic stress followed by a novel
(heterotypic) stressor induces facilitation.
Forebrain limbic region  BST  PVN
dorsomedial nucleus (dm)
&
fusiform nucleus (fu)
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Located in the anterior
division of the BST
Ventral to the anterior
commissure
Heavy projections to
the medial parvocellular
PVN
Relay stress-excitatory
information to the PVN
Hypothesis
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The contribution of the BST to chronic stress?
The BST dm/fu nuclei are necessary for
sensitization of HPA axis response after
chronic stress?
Chronic variable stress (CVS) paradigm  a
novel restraint challenge  assess CVSinduced adaptations in HPA axis reactivity
Materials and Methods
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Subjects: SD rats
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Bilateral microinjections of ibotenate or saline into
the anterior BST
Four groups: sham non-CVS, sham CVS,
lesion non-CVS, lesion CVS
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Twice-daily exposure to alternating stressors for
14 days
Morning stressor, afternoon stressor and
occational overnight stressor
CVS stressors: hypoxia, cold stress, rotation
stress, warm swim, cold swim, overnight social
isolation, overnight social crowding
Acute novel restraint stress
protocol
day after the cessation of CVS
placement in restraint tubes
blood sampling
20 min restraints tress
Blood sampling
returned to home cage
Blood sampling
(40 min from the onset of the restraint stress)
decapitation, collecting blood sample
(60min)
Measurements
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RIA
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Lesion verification
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Nissl staining of cells
Neuronal nuclei (NeuN) immunolabeling
In situ hybridization and image analysis
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measure plasma cort and ACTH level
Measure AVP, CRH and c-fos mRNA levels in
the PVN
Statistical analysis
Results
Lesions of the BST dm/fu nuclei
Anterior BST lesions were
centered ventral to the
anterior commissure
at approximately AP 0.10mm from bregma.
Body and organ weights
Body weight
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Destruction of the BST dm/fu is not sufficient
to alter the consequences of chronic stress on
body weight.
Body and organ weights
Organ weights
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CVS induces adrenal hypertrophy /hyperplasia
No effects of lesion on adrenal weights
No effects of lesion on thymus weights
Main effects of CVS on raw thymus weight but not on
thymus weight adj. for body weight
Plasma ACTH levels
Plasma cort levels
c-fos mRNA expression in the PVN
CRF mRNA expression in the PVN
AVP mRNA expression in the PVN
Discussion
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The BSTdm/fu act as activators of the HPA
axis response to acute stress, but are also
involved in inhibitory regulation of HPA
axis reactivity after chronic stress.
Disruption of the BST dm/fu nuclei does
not affect the development of steady-state
changes in HPA function engendered by
chronic stress.
Several possible mechanisms
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Acute and chronic stress may recruit different
populations of BST dm/fu neurons:
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CRH, Glu, GABA.
Inputs from brainstem and limbic regions
might project to separate pools of neurons in
the BST dm/fu.
Interruption of BST dm/fu input to the PVN or
PVN-projecting structures may permit a
compensatory enhancement of inputs that
are sensitive to the effects of chronic stress.