X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Schulz, Stefan  (5)
  • Linguistics  (5)
  • 1
    Online Resource
    Online Resource
    Somatostatin Receptor 2 Is Activated in Cortical Neurons and Contributes to Neurodegeneration after Focal Ischemia
    Society for Neuroscience ; 2004
    In:  The Journal of Neuroscience Vol. 24, No. 50 ( 2004-12-15), p. 11404-11415
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 24, No. 50 ( 2004-12-15), p. 11404-11415
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.3834-04.2004
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2004
    detail.hit.zdb_id: 1475274-8
    SSG: 12
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 2
    Online Resource
    Online Resource
    CXCR4 Regulates Interneuron Migration in the Developing Neocortex
    Society for Neuroscience ; 2003
    In:  The Journal of Neuroscience Vol. 23, No. 12 ( 2003-06-15), p. 5123-5130
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 23, No. 12 ( 2003-06-15), p. 5123-5130
    Abstract: The chemotactic factors directing interneuron migration during cerebrocortical development are essentially unknown. Here we identify the CXC chemokine receptor 4 (CXCR4) in interneuron precursors migrating from the basal forebrain to the neocortex and demonstrate that stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant for isolated striatal precursors. In addition, we show that CXCR4 is present in early generated Cajal-Retzius cells of the cortical marginal zone. In mice with a null mutation in CXCR4 or SDF-1, interneurons were severely underrepresented in the superficial layers and ectopically placed in the deep layers of the neocortex. In contrast, the submeningeal positioning of Cajal-Retzius cells was unaffected. Thus, our findings suggest that SDF-1, which is highly expressed in the embryonic leptomeninx, selectively regulates migration and layer-specific integration of CXCR4-expressing interneurons during neocortical development.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.23-12-05123.2003
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2003
    detail.hit.zdb_id: 1475274-8
    SSG: 12
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 3
    Online Resource
    Online Resource
    Tonic Activation of CXC Chemokine Receptor 4 in Immature Granule Cells Supports Neurogenesis in the Adult Dentate Gyrus
    Society for Neuroscience ; 2008
    In:  The Journal of Neuroscience Vol. 28, No. 17 ( 2008-04-23), p. 4488-4500
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 28, No. 17 ( 2008-04-23), p. 4488-4500
    Abstract: Stromal-cell-derived factor-1 (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) play a well-established role during embryonic development of dentate gyrus granule cells. However, little is known about the regulation and function of CXCR4 in the postnatal dentate gyrus. Here, we identify a striking mismatch between intense CXCR4 mRNA and limited CXCR4 protein expression in adult rat subgranular layer (SGL) neurons. We demonstrate that CXCR4 protein expression in SGL neurons is progressively lost during postnatal day 15 (P15) to P21. This loss of CXCR4 protein expression was paralleled by a reduction in the number of SDF-1-responsive SGL neurons and a massive upregulation of SDF-1 mRNA in granule cells. Intraventricular infusion of the CXCR4-antagonist AMD3100 dramatically increased CXCR4 protein expression in SGL neurons, suggesting that CXCR4 is tonically activated and downregulated by endogenous SDF-1. Infusion of AMD3100 also facilitated detection of CXCR4 protein in bromodeoxyuridine-, nestin-, and doublecortin-labeled cells and showed that the vast majority of adult-born granule cells transiently expressed CXCR4. Chronic AMD3100 administration impaired formation of new granule cells as well as neurogenesis-dependent long-term recognition of novel objects. Therefore, our findings suggest that tonic activation of CXCR4 in newly formed granule cells by endogenous SDF-1 is essential for neurogenesis-dependent long-term memory in the adult hippocampus.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.4721-07.2008
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2008
    detail.hit.zdb_id: 1475274-8
    SSG: 12
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 4
    Online Resource
    Online Resource
    A Dual Role for the SDF-1/CXCR4 Chemokine Receptor System in Adult Brain: Isoform-Selective Regulation of SDF-1 Expression Modulates CXCR4-Dependent Neuronal Plasticity and Cerebral Leukocyte Recruitment after Focal Ischemia
    Society for Neuroscience ; 2002
    In:  The Journal of Neuroscience Vol. 22, No. 14 ( 2002-07-15), p. 5865-5878
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 22, No. 14 ( 2002-07-15), p. 5865-5878
    Abstract: The chemoattractant stromal cell-derived factor-1 (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) are key modulators of immune function. In the developing brain, SDF-1 is crucial for neuronal guidance; however, cerebral functions of SDF-1/CXCR4 in adulthood are unclear. Here, we examine the cellular expression of SDF-1 isoforms and CXCR4 in the brain of mice receiving systemic lipopolysaccharide (LPS) or permanent focal cerebral ischemia. CXCR4 mRNA was constitutively expressed in cortical and hippocampal neurons and ependymal cells. Hippocampal neurons targeted the CXCR4 receptor to their somatodendritic and axonal compartments. In cortex and hippocampus, CXCR4-expressing neurons exhibited an overlapping distribution with neurons expressing SDF-1 transcripts. Although neurons synthesized SDF-1α mRNA, the SDF-1β isoform was selectively expressed by endothelial cells of cerebral microvessels. LPS stimulation dramatically decreased endothelial SDF-1β mRNA expression throughout the forebrain but did not affect neuronal SDF-1α. After focal cerebral ischemia, SDF-1β expression was selectively increased in endothelial cells of penumbral blood vessels and decreased in endothelial cells of nonlesioned brain areas. In the penumbra, SDF-1β upregulation was associated with a concomitant infiltration of CXCR4-expressing peripheral blood cells, including macrophages. Neuronal SDF-1α was transiently downregulated and neuronal CXCR4 was transiently upregulated in the nonlesioned cerebral cortex in response to ischemia. Although endothelial SDF-1β may control cerebral infiltration of CXCR4-carrying leukocytes during cerebral ischemia, the neuronal SDF-1α/CXCR4 system may contribute to ischemia-induced neuronal plasticity. Thus, the isoform-specific regulation of SDF-1 expression modulates neurotransmission and cerebral infiltration via distinct CXCR4-dependent pathways.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.22-14-05865.2002
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2002
    detail.hit.zdb_id: 1475274-8
    SSG: 12
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 5
    Online Resource
    Online Resource
    Analgesic Tolerance to High-Efficacy Agonists But Not to Morphine Is Diminished in Phosphorylation-Deficient S375A μ-Opioid Receptor Knock-In Mice
    Society for Neuroscience ; 2011
    In:  The Journal of Neuroscience Vol. 31, No. 39 ( 2011-09-28), p. 13890-13896
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 31, No. 39 ( 2011-09-28), p. 13890-13896
    Abstract: Morphine is one of the most potent analgesic drugs. However, the utility of morphine in the management of chronic pain is limited by its rapid development of tolerance. Morphine exerts all of its pharmacological effects via the μ-opioid receptor. In many systems, tolerance is associated with phosphorylation and desensitization of G-protein-coupled receptors (GPCRs). In case of the μ-opioid receptor, phosphorylation occurs in an agonist-selective manner. High-efficacy agonists such as [ d -Ala 2 -MePhe 4 -Gly-ol]enkephalin (DAMGO), fentanyl, or etonitazene stimulate the phosphorylation of both C-terminal threonine 370 (T370) and serine 375 (S375). In contrast, morphine promotes the phosphorylation of S375 but fails to stimulate T370 phosphorylation. Here, we have assessed the contribution of S375 phosphorylation to the development of antinociceptive tolerance to high- and low-efficacy μ agonists in vivo . We show that S375 phosphorylation of the μ-opioid receptor occurs in intact mouse brain in a dose-dependent manner after administration of morphine, fentanyl, or etonitazene. In knock-in mice expressing the phosphorylation-deficient S375A mutant of the μ-opioid receptor, morphine and fentanyl exhibited greater dose-dependent antinociceptive responses than in wild-type mice. However, acute and chronic tolerance to morphine was retained in S375A mutant mice. In contrast, antinociceptive tolerance after repeated subcutaneous application of etonitazene or repeated intracerebroventricular application of DAMGO was diminished. Thus, tolerance to μ agonists with different efficacies develops through distinct pathways. Whereas tolerance induced by DAMGO or etonitazene requires agonist-driven phosphorylation of S375, the development and maintenance of antinociceptive tolerance to morphine occurs independent of S375 phosphorylation.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.2304-11.2011
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2011
    detail.hit.zdb_id: 1475274-8
    SSG: 12
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
Nothing or not found what you are looking for? Please check your search query or use the Interlibrary Loan Search.
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages