Sequence of stress-induced alterations in indices of synaptic and transcriptional activation in parvocellular neurosecretory neurons

K. Kovács, P. E. Sawchenko

Research output: Contribution to journalArticle

279 Citations (Scopus)

Abstract

Immediate-early genes (IEGs) are widely used to mark endocrine hypothalamic neurons that are activated in response to stress, yet their relationship to the transcriptional control of relevant effector molecule expression is unclear. Acute ether stress provokes increased adrenocorticotropic hormone (ACTH) and corticosterone secretion that peaks at 5 and 30 min, respectively, after the challenge. Using probes complementary to intronic sequences of genes encoding ACTH secretagogues in parvocellular neurosecretory neurons of the paraventricular nucleus, we found these events to be accompanied by rapid and transient increases in corticotropin-releasing factor heteronuclear RNA (CRF hnRNA; peak at 5 min) and by a delayed upregulation of arginine vasopressin (AVP) hnRNA (120 min). To identify candidate mechanisms regulating peptide expression, we followed the timing of ether effects on representatives of three transcription factor classes: IEGs [c-fos and nerve growth factor I-B (NGFI-B)], a POU-domain factor (Brn-2), and the cAMP response element-binding protein (CREB), using antisera specific to its transcriptionally active, phosphorylated form (pCREB). After ether exposure, c-fos and NGFI-B mRNA induction were maximal at 30-60 min, whereas Fos protein peaked at 60-120 min. Brn-2 mRNA was expressed constitutively in the PVH and was unresponsive to stress. By contrast, pCREB was induced in parvocellular neurons with a time course parallel to that of CRF hnRNA expression. Stress-induced transcriptional activation of the CRF and AVP genes in hypophysiotropic neurons follows distinct time courses that are compatible with control mechanisms involving phosphorylation events and de novo protein synthesis, respectively.

Original languageEnglish
Pages (from-to)262-273
Number of pages12
JournalJournal of Neuroscience
Volume16
Issue number1
Publication statusPublished - Jan 1 1996

Fingerprint

Ether
Transcriptional Activation
Immediate-Early Genes
Arginine Vasopressin
Nerve Growth Factor
Neurons
Adrenocorticotropic Hormone
POU Domain Factors
Cyclic AMP Response Element-Binding Protein
Neuroendocrine Cells
Messenger RNA
Paraventricular Hypothalamic Nucleus
Corticotropin-Releasing Hormone
Corticosterone
Genes
Immune Sera
Proteins
Transcription Factors
Up-Regulation
Phosphorylation

Keywords

  • arginine vasopressin
  • c- fos
  • cAMP
  • corticotropin-releasing factor
  • hypothalamo-pituitary-adrenal axis
  • neurosecretory neurons
  • stress

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Sequence of stress-induced alterations in indices of synaptic and transcriptional activation in parvocellular neurosecretory neurons. / Kovács, K.; Sawchenko, P. E.

In: Journal of Neuroscience, Vol. 16, No. 1, 01.01.1996, p. 262-273.

Research output: Contribution to journalArticle

@article{6a4e5896852744e984e82e30a67e5820,
title = "Sequence of stress-induced alterations in indices of synaptic and transcriptional activation in parvocellular neurosecretory neurons",
abstract = "Immediate-early genes (IEGs) are widely used to mark endocrine hypothalamic neurons that are activated in response to stress, yet their relationship to the transcriptional control of relevant effector molecule expression is unclear. Acute ether stress provokes increased adrenocorticotropic hormone (ACTH) and corticosterone secretion that peaks at 5 and 30 min, respectively, after the challenge. Using probes complementary to intronic sequences of genes encoding ACTH secretagogues in parvocellular neurosecretory neurons of the paraventricular nucleus, we found these events to be accompanied by rapid and transient increases in corticotropin-releasing factor heteronuclear RNA (CRF hnRNA; peak at 5 min) and by a delayed upregulation of arginine vasopressin (AVP) hnRNA (120 min). To identify candidate mechanisms regulating peptide expression, we followed the timing of ether effects on representatives of three transcription factor classes: IEGs [c-fos and nerve growth factor I-B (NGFI-B)], a POU-domain factor (Brn-2), and the cAMP response element-binding protein (CREB), using antisera specific to its transcriptionally active, phosphorylated form (pCREB). After ether exposure, c-fos and NGFI-B mRNA induction were maximal at 30-60 min, whereas Fos protein peaked at 60-120 min. Brn-2 mRNA was expressed constitutively in the PVH and was unresponsive to stress. By contrast, pCREB was induced in parvocellular neurons with a time course parallel to that of CRF hnRNA expression. Stress-induced transcriptional activation of the CRF and AVP genes in hypophysiotropic neurons follows distinct time courses that are compatible with control mechanisms involving phosphorylation events and de novo protein synthesis, respectively.",
keywords = "arginine vasopressin, c- fos, cAMP, corticotropin-releasing factor, hypothalamo-pituitary-adrenal axis, neurosecretory neurons, stress",
author = "K. Kov{\'a}cs and Sawchenko, {P. E.}",
year = "1996",
month = "1",
day = "1",
language = "English",
volume = "16",
pages = "262--273",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "1",

}

TY - JOUR

T1 - Sequence of stress-induced alterations in indices of synaptic and transcriptional activation in parvocellular neurosecretory neurons

AU - Kovács, K.

AU - Sawchenko, P. E.

PY - 1996/1/1

Y1 - 1996/1/1

N2 - Immediate-early genes (IEGs) are widely used to mark endocrine hypothalamic neurons that are activated in response to stress, yet their relationship to the transcriptional control of relevant effector molecule expression is unclear. Acute ether stress provokes increased adrenocorticotropic hormone (ACTH) and corticosterone secretion that peaks at 5 and 30 min, respectively, after the challenge. Using probes complementary to intronic sequences of genes encoding ACTH secretagogues in parvocellular neurosecretory neurons of the paraventricular nucleus, we found these events to be accompanied by rapid and transient increases in corticotropin-releasing factor heteronuclear RNA (CRF hnRNA; peak at 5 min) and by a delayed upregulation of arginine vasopressin (AVP) hnRNA (120 min). To identify candidate mechanisms regulating peptide expression, we followed the timing of ether effects on representatives of three transcription factor classes: IEGs [c-fos and nerve growth factor I-B (NGFI-B)], a POU-domain factor (Brn-2), and the cAMP response element-binding protein (CREB), using antisera specific to its transcriptionally active, phosphorylated form (pCREB). After ether exposure, c-fos and NGFI-B mRNA induction were maximal at 30-60 min, whereas Fos protein peaked at 60-120 min. Brn-2 mRNA was expressed constitutively in the PVH and was unresponsive to stress. By contrast, pCREB was induced in parvocellular neurons with a time course parallel to that of CRF hnRNA expression. Stress-induced transcriptional activation of the CRF and AVP genes in hypophysiotropic neurons follows distinct time courses that are compatible with control mechanisms involving phosphorylation events and de novo protein synthesis, respectively.

AB - Immediate-early genes (IEGs) are widely used to mark endocrine hypothalamic neurons that are activated in response to stress, yet their relationship to the transcriptional control of relevant effector molecule expression is unclear. Acute ether stress provokes increased adrenocorticotropic hormone (ACTH) and corticosterone secretion that peaks at 5 and 30 min, respectively, after the challenge. Using probes complementary to intronic sequences of genes encoding ACTH secretagogues in parvocellular neurosecretory neurons of the paraventricular nucleus, we found these events to be accompanied by rapid and transient increases in corticotropin-releasing factor heteronuclear RNA (CRF hnRNA; peak at 5 min) and by a delayed upregulation of arginine vasopressin (AVP) hnRNA (120 min). To identify candidate mechanisms regulating peptide expression, we followed the timing of ether effects on representatives of three transcription factor classes: IEGs [c-fos and nerve growth factor I-B (NGFI-B)], a POU-domain factor (Brn-2), and the cAMP response element-binding protein (CREB), using antisera specific to its transcriptionally active, phosphorylated form (pCREB). After ether exposure, c-fos and NGFI-B mRNA induction were maximal at 30-60 min, whereas Fos protein peaked at 60-120 min. Brn-2 mRNA was expressed constitutively in the PVH and was unresponsive to stress. By contrast, pCREB was induced in parvocellular neurons with a time course parallel to that of CRF hnRNA expression. Stress-induced transcriptional activation of the CRF and AVP genes in hypophysiotropic neurons follows distinct time courses that are compatible with control mechanisms involving phosphorylation events and de novo protein synthesis, respectively.

KW - arginine vasopressin

KW - c- fos

KW - cAMP

KW - corticotropin-releasing factor

KW - hypothalamo-pituitary-adrenal axis

KW - neurosecretory neurons

KW - stress

UR - http://www.scopus.com/inward/record.url?scp=0030070524&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030070524&partnerID=8YFLogxK

M3 - Article

VL - 16

SP - 262

EP - 273

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 1

ER -