Adult glucocorticoid receptor mRNA expression volatility in response to an acute stressor and juvenile CSF corticotropin-releasing factor

A pilot neurodevelopmental study

Shariful A. Syed, Eric L P Smith, Olcay Batuman, Leonard A. Rosenblum, Michael J. Owens, Charles Nemeroff, Jeremy D. Coplan

Research output: Contribution to journalArticle

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Abstract

Introduction Early life stress (ELS) has been shown to play a role in establishing persistent maladaptive HPA axis modifications that may contribute to the pathogenesis of mood and anxiety disorders. Central glucocorticoid receptor (GR) messenger RNA (mRNA) expression may facilitate (mal)adaptive responsivity to ELS. The role of adult monocytic GR mRNA expression, a putative CNS proxy, during acute stress exposure was explored as well as the ELS marker, juvenile cerebrospinal fluid (CSF) corticotropin-releasing factor. Methods Six adult macaques (three of which were exposed to variable foraging demand, a form of ELS) underwent acute restraint. Baseline GR expression and plasma cortisol concentrations were separately measured followed by subsequent measurements following stress completion (t = 0 min, 4 h, 5 days and 7 days). Juvenile CSF CRF concentrations were available in five subjects to determine their developmental association with GR expression in response to stress. Results As expected acute restraint stress produced a significant increase in plasma cortisol concentrations most robustly observed at 4 h post-stress time point. There was a significant juvenile CSF CRF concentration x time interaction in predicting adult GR mRNA expression in response to stress (partial η2 = 0.80). During acute stress juvenile CRF concentrations negatively predicted GR expression and during recovery, “flipped” to positively predict expression. Juvenile CSF CRF concentrations positively correlated with the volatility of adult GR mRNA expression. Conclusions During acute stress, relatively high CSF CRF concentrations are associated with relatively rapid reductions in GR expression. Return to an ambient post-stress state was characterized by a direct relationship, consistent with increased HPA axis restraint in high CRF subjects. An ELS-associated allostatic adaptation suggests relative elevations of juvenile CSF CRF concentration set the stage for a relative hyper-volatility of adult GR mRNA expression in response to acute stress with potential long-term implications for HPA axis regulation.

Original languageEnglish (US)
Pages (from-to)20-25
Number of pages6
JournalNeuroscience Letters
Volume647
DOIs
StatePublished - Apr 24 2017

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Volatilization
Corticotropin-Releasing Hormone
Glucocorticoid Receptors
Cerebrospinal Fluid
Messenger RNA
Psychological Stress
Hydrocortisone
Macaca
Proxy
Anxiety Disorders
Mood Disorders

ASJC Scopus subject areas

  • Neuroscience(all)

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Adult glucocorticoid receptor mRNA expression volatility in response to an acute stressor and juvenile CSF corticotropin-releasing factor : A pilot neurodevelopmental study. / Syed, Shariful A.; Smith, Eric L P; Batuman, Olcay; Rosenblum, Leonard A.; Owens, Michael J.; Nemeroff, Charles; Coplan, Jeremy D.

In: Neuroscience Letters, Vol. 647, 24.04.2017, p. 20-25.

Research output: Contribution to journalArticle

Syed, Shariful A. ; Smith, Eric L P ; Batuman, Olcay ; Rosenblum, Leonard A. ; Owens, Michael J. ; Nemeroff, Charles ; Coplan, Jeremy D. / Adult glucocorticoid receptor mRNA expression volatility in response to an acute stressor and juvenile CSF corticotropin-releasing factor : A pilot neurodevelopmental study. In: Neuroscience Letters. 2017 ; Vol. 647. pp. 20-25.
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abstract = "Introduction Early life stress (ELS) has been shown to play a role in establishing persistent maladaptive HPA axis modifications that may contribute to the pathogenesis of mood and anxiety disorders. Central glucocorticoid receptor (GR) messenger RNA (mRNA) expression may facilitate (mal)adaptive responsivity to ELS. The role of adult monocytic GR mRNA expression, a putative CNS proxy, during acute stress exposure was explored as well as the ELS marker, juvenile cerebrospinal fluid (CSF) corticotropin-releasing factor. Methods Six adult macaques (three of which were exposed to variable foraging demand, a form of ELS) underwent acute restraint. Baseline GR expression and plasma cortisol concentrations were separately measured followed by subsequent measurements following stress completion (t = 0 min, 4 h, 5 days and 7 days). Juvenile CSF CRF concentrations were available in five subjects to determine their developmental association with GR expression in response to stress. Results As expected acute restraint stress produced a significant increase in plasma cortisol concentrations most robustly observed at 4 h post-stress time point. There was a significant juvenile CSF CRF concentration x time interaction in predicting adult GR mRNA expression in response to stress (partial η2 = 0.80). During acute stress juvenile CRF concentrations negatively predicted GR expression and during recovery, “flipped” to positively predict expression. Juvenile CSF CRF concentrations positively correlated with the volatility of adult GR mRNA expression. Conclusions During acute stress, relatively high CSF CRF concentrations are associated with relatively rapid reductions in GR expression. Return to an ambient post-stress state was characterized by a direct relationship, consistent with increased HPA axis restraint in high CRF subjects. An ELS-associated allostatic adaptation suggests relative elevations of juvenile CSF CRF concentration set the stage for a relative hyper-volatility of adult GR mRNA expression in response to acute stress with potential long-term implications for HPA axis regulation.",
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T1 - Adult glucocorticoid receptor mRNA expression volatility in response to an acute stressor and juvenile CSF corticotropin-releasing factor

T2 - A pilot neurodevelopmental study

AU - Syed, Shariful A.

AU - Smith, Eric L P

AU - Batuman, Olcay

AU - Rosenblum, Leonard A.

AU - Owens, Michael J.

AU - Nemeroff, Charles

AU - Coplan, Jeremy D.

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N2 - Introduction Early life stress (ELS) has been shown to play a role in establishing persistent maladaptive HPA axis modifications that may contribute to the pathogenesis of mood and anxiety disorders. Central glucocorticoid receptor (GR) messenger RNA (mRNA) expression may facilitate (mal)adaptive responsivity to ELS. The role of adult monocytic GR mRNA expression, a putative CNS proxy, during acute stress exposure was explored as well as the ELS marker, juvenile cerebrospinal fluid (CSF) corticotropin-releasing factor. Methods Six adult macaques (three of which were exposed to variable foraging demand, a form of ELS) underwent acute restraint. Baseline GR expression and plasma cortisol concentrations were separately measured followed by subsequent measurements following stress completion (t = 0 min, 4 h, 5 days and 7 days). Juvenile CSF CRF concentrations were available in five subjects to determine their developmental association with GR expression in response to stress. Results As expected acute restraint stress produced a significant increase in plasma cortisol concentrations most robustly observed at 4 h post-stress time point. There was a significant juvenile CSF CRF concentration x time interaction in predicting adult GR mRNA expression in response to stress (partial η2 = 0.80). During acute stress juvenile CRF concentrations negatively predicted GR expression and during recovery, “flipped” to positively predict expression. Juvenile CSF CRF concentrations positively correlated with the volatility of adult GR mRNA expression. Conclusions During acute stress, relatively high CSF CRF concentrations are associated with relatively rapid reductions in GR expression. Return to an ambient post-stress state was characterized by a direct relationship, consistent with increased HPA axis restraint in high CRF subjects. An ELS-associated allostatic adaptation suggests relative elevations of juvenile CSF CRF concentration set the stage for a relative hyper-volatility of adult GR mRNA expression in response to acute stress with potential long-term implications for HPA axis regulation.

AB - Introduction Early life stress (ELS) has been shown to play a role in establishing persistent maladaptive HPA axis modifications that may contribute to the pathogenesis of mood and anxiety disorders. Central glucocorticoid receptor (GR) messenger RNA (mRNA) expression may facilitate (mal)adaptive responsivity to ELS. The role of adult monocytic GR mRNA expression, a putative CNS proxy, during acute stress exposure was explored as well as the ELS marker, juvenile cerebrospinal fluid (CSF) corticotropin-releasing factor. Methods Six adult macaques (three of which were exposed to variable foraging demand, a form of ELS) underwent acute restraint. Baseline GR expression and plasma cortisol concentrations were separately measured followed by subsequent measurements following stress completion (t = 0 min, 4 h, 5 days and 7 days). Juvenile CSF CRF concentrations were available in five subjects to determine their developmental association with GR expression in response to stress. Results As expected acute restraint stress produced a significant increase in plasma cortisol concentrations most robustly observed at 4 h post-stress time point. There was a significant juvenile CSF CRF concentration x time interaction in predicting adult GR mRNA expression in response to stress (partial η2 = 0.80). During acute stress juvenile CRF concentrations negatively predicted GR expression and during recovery, “flipped” to positively predict expression. Juvenile CSF CRF concentrations positively correlated with the volatility of adult GR mRNA expression. Conclusions During acute stress, relatively high CSF CRF concentrations are associated with relatively rapid reductions in GR expression. Return to an ambient post-stress state was characterized by a direct relationship, consistent with increased HPA axis restraint in high CRF subjects. An ELS-associated allostatic adaptation suggests relative elevations of juvenile CSF CRF concentration set the stage for a relative hyper-volatility of adult GR mRNA expression in response to acute stress with potential long-term implications for HPA axis regulation.

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