Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
50
pubmed:dateCreated
2004-12-16
pubmed:abstractText
The hypothalamic neuropeptides hypocretins (orexins) play a crucial role in the stability of arousal and alertness. We tested whether the hypocretinergic system is a critical component of the stress response activated by the corticotropin-releasing factor (CRF). Our results show that CRF-immunoreactive terminals make direct contact with hypocretin-expressing neurons in the lateral hypothalamus and that numerous hypocretinergic neurons express the CRF-R1/2 receptors. We also demonstrate that application of CRF to hypothalamic slices containing identified hypocretin neurons depolarizes membrane potential and increases firing rate in a subpopulation of hypocretinergic cells. CRF-induced depolarization was tetrodotoxin insensitive and was blocked by the peptidergic CRF-R1 antagonist astressin. Moreover, activation of hypocretinergic neurons in response to acute stress was severely impaired in CRF-R1 knock-out mice. Together, our data provide evidence of a direct neuroanatomical and physiological input from CRF peptidergic system onto hypocretin neurons. We propose that, after stressor stimuli, CRF stimulates the release of hypocretins and that this circuit contributes to activation and maintenance of arousal associated with the stress response.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11439-48
pubmed:dateRevised
2011-8-1
pubmed:meshHeading
pubmed-meshheading:15601950-Action Potentials, pubmed-meshheading:15601950-Animals, pubmed-meshheading:15601950-Arousal, pubmed-meshheading:15601950-Brain, pubmed-meshheading:15601950-Brain Chemistry, pubmed-meshheading:15601950-Corticotropin-Releasing Hormone, pubmed-meshheading:15601950-Female, pubmed-meshheading:15601950-Hypothalamus, pubmed-meshheading:15601950-Immunohistochemistry, pubmed-meshheading:15601950-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:15601950-Male, pubmed-meshheading:15601950-Membrane Potentials, pubmed-meshheading:15601950-Mice, pubmed-meshheading:15601950-Mice, Knockout, pubmed-meshheading:15601950-Neural Pathways, pubmed-meshheading:15601950-Neurons, pubmed-meshheading:15601950-Neuropeptides, pubmed-meshheading:15601950-Receptors, Corticotropin-Releasing Hormone, pubmed-meshheading:15601950-Receptors, G-Protein-Coupled, pubmed-meshheading:15601950-Receptors, Neuropeptide, pubmed-meshheading:15601950-Recombinant Fusion Proteins, pubmed-meshheading:15601950-Stress, Physiological
pubmed:year
2004
pubmed:articleTitle
Interaction between the corticotropin-releasing factor system and hypocretins (orexins): a novel circuit mediating stress response.
pubmed:affiliation
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural