Linked Life Data

15601946

Source:http://linkedlifedata.com/resource/pubmed/id/15601946

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
50
pubmed:dateCreated
2004-12-16
pubmed:abstractText
Somatostatin receptor 2 (SSTR2) mediates neuromodulatory signals of somatostatin and cortistatin in the cerebral cortex. Recently, SSTR2 has been shown to enhance conserved death ligand- and mitochondria-mediated apoptotic pathways in non-neuronal cells. Whether somatostatin receptors are activated in cerebrocortical neurons and contribute to neurodegeneration after experimental focal ischemia was unknown until now. Here we examined internalization of SSTR2 in a rat model of middle cerebral artery occlusion (MCAO) by confocal microscopy. At 3 and 6 hr after MCAO, SSTR2 was internalized excessively in cerebrocortical neurons adjacent to the infarct, which was prevented by intracerebroventricular application of the SSTR2-selective antagonist BIM-23627. SSTR2 internalization was associated with a transient depletion of somatostatin from axonal terminals and increased expression of SSTR2 mRNA. The initial loss of somatostatin was followed by an increase in somatostatin mRNA levels, whereas cortistatin mRNA expression was decreased. In SSTR2-deficient mice with lacZ under the control of the SSTR2 promoter, MCAO-induced upregulation of SSTR2 gene expression was less pronounced than in wild types. SSTR2-deficient mice exhibited a 40% reduction of infarct size after permanent distal MCAO and a 63% reduction after transient proximal MCAO. In summary, we provide direct evidence for activation of SSTR2 by an endogenous ligand after focal ischemia. Activation of functional SSTR2 receptors contributes to increased SSTR2 gene expression and postischemic neurodegeneration.
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
11404-15
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15601946-Animals, pubmed-meshheading:15601946-Axons, pubmed-meshheading:15601946-Brain Ischemia, pubmed-meshheading:15601946-Cell Line, pubmed-meshheading:15601946-Cerebral Cortex, pubmed-meshheading:15601946-Cerebral Infarction, pubmed-meshheading:15601946-Fluorescent Antibody Technique, pubmed-meshheading:15601946-Humans, pubmed-meshheading:15601946-Immunoenzyme Techniques, pubmed-meshheading:15601946-In Situ Hybridization, pubmed-meshheading:15601946-Male, pubmed-meshheading:15601946-Mice, pubmed-meshheading:15601946-Mice, Inbred C57BL, pubmed-meshheading:15601946-Mice, Knockout, pubmed-meshheading:15601946-Microscopy, Confocal, pubmed-meshheading:15601946-Nerve Degeneration, pubmed-meshheading:15601946-Nerve Tissue Proteins, pubmed-meshheading:15601946-Neurons, pubmed-meshheading:15601946-Neuropeptides, pubmed-meshheading:15601946-Peptides, pubmed-meshheading:15601946-Rats, pubmed-meshheading:15601946-Rats, Long-Evans, pubmed-meshheading:15601946-Receptors, Somatostatin, pubmed-meshheading:15601946-Somatostatin, pubmed-meshheading:15601946-Up-Regulation
pubmed:year
2004
pubmed:articleTitle
Somatostatin receptor 2 is activated in cortical neurons and contributes to neurodegeneration after focal ischemia.
pubmed:affiliation
Institute of Pharmacology and Toxicology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany. ralf.stumm@medizin.uni-magdeburg.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't