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The Anteroventral BST Differentially Regulates HPA Axis Responses to Acute and Chronic Stress

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. Decreases body weight and food intake Induces adrenal hypertrophy Involution of thymus

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The Anteroventral BST Differentially Regulates HPA Axis Responses to Acute and Chronic Stress

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  1. 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.

  2. IntroductionChronic Stress • 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 • (in some stress models) • Increased circulating glucocorticoids

  3. The comparison between acute and chronic stress regarding the HPA axis • 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.

  4. Different brain circuitries are involved in acute and chronic stress responses. • Paraventricular thalamus regulate HPA axis responses to chronic stressors. • Chronic stress can produce enhancement of HPA axis responses to new stressors. • Repeated experience with the same (homotypic) stressor produces habituation of HPA axis responses. • Repeated homotypic stress followed by a novel (heterotypic) stressor induces facilitation.

  5. Forebrain limbic region  BST  PVN

  6. dorsomedial nucleus (dm) & fusiform nucleus (fu) • 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

  7. Hypothesis 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 CVS-induced adaptations in HPA axis reactivity

  8. Materials and Methods • Subjects: SD rats • Bilateral microinjections of ibotenate or saline into the anterior BST • Four groups: sham non-CVS, sham CVS, lesion non-CVS, lesion CVS • 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

  9. 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)

  10. Measurements • RIA • measure plasma cort and ACTH level • Lesion verification • Nissl staining of cells • Neuronal nuclei (NeuN) immunolabeling • In situ hybridization and image analysis • Measure AVP, CRH and c-fos mRNA levels in the PVN • Statistical analysis

  11. ResultsLesions of the BST dm/fu nuclei Anterior BST lesions were centered ventral to the anterior commissure at approximately AP -0.10mm from bregma.

  12. Body and organ weightsBody weight • Destruction of the BST dm/fu is not sufficient to alter the consequences of chronic stress on body weight.

  13. Body and organ weights Organ weights • 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

  14. Plasma ACTH levels

  15. Plasma cort levels

  16. c-fos mRNA expression in the PVN

  17. CRF mRNA expression in the PVN

  18. AVP mRNA expression in the PVN

  19. Discussion 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.

  20. Several possible mechanisms • Acute and chronic stress may recruit different populations of BST dm/fu neurons: • 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.

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