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Hippocampal Cannabinoid-1 Receptor Upregulation Upon Endothelin-B Receptor Deficiency: A Neuroprotective Substitution Effect?

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Abstract

Endothelin (ETB)-receptors mediate anti-apoptotic actions. Lack of functional ETB-receptors leads to increased neuronal apoptosis in the hippocampus. The increased apoptosis must be compensated by other mechanisms, however, as ETB-deficient rats display normal overall brain morphology. To illuminate on brain plasticity in ETB-receptor deficiency, we studied the expression and function of another neuroprotective system, the cannabinoid CB1-receptors, in ETB-deficient hippocampus. We show that CB1 expression in hippocampus increases postnatally in all rats but that the increase in CB1-receptor expression is significantly higher in ETB-deficient compared to wildtype littermates. Neuronal apoptosis decreases during brain maturation but remains on a significantly higher level in the ETB-deficient compared to wildtype dentate. When investigating survival of hippocampal neurons in culture, we found significant protection against hypoxia-induced cell death with CB1-analogs (noladin, (9-tetrahydrocannabinol) only in ETB-deficient neurons. We suggest that CB1-receptor upregulation in the ETB-mutant hippocampus reflects an attempt to compensate for the lack of ETB-receptors.

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Authors and Affiliations

  1. Division of Clinical Neuroscience, Max-Planck-Institute for Experimental Medicine, Göttingen, Germany

    Christian Unzicker, Heike Erberich, Gabriella Moldrich, Helge Woldt, Hannelore Ehrenreich & Anna-Leena Sirén

  2. Centre for Statistics and Institute for Statistics and Econometrics, Georg-August-University, Göttingen, Germany

    Jan Bulla

  3. Pharmacy School Department of Medical Chemistry and Natural Products, Hebrew University Medical Faculty, Jerusalem, Israel

    Raphael Mechoulam

  4. Section of Experimental Neurosurgery, Department of Neurosurgery, Julius-Maximilians-University, Würzburg, Germany

    Anna-Leena Sirén

  5. Max-Planck-Institute for Experimental Medicine, Hermann-Rein-Str. 3, D-37075, Göttingen, Germany

    Hannelore Ehrenreich

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  1. Christian Unzicker
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  2. Heike Erberich
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  3. Gabriella Moldrich
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  4. Helge Woldt
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  6. Raphael Mechoulam
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  7. Hannelore Ehrenreich
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  8. Anna-Leena Sirén
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Correspondence to Hannelore Ehrenreich.

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Special issue dedicated to Dr. Bernd Hamprecht

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Unzicker, C., Erberich, H., Moldrich, G. et al. Hippocampal Cannabinoid-1 Receptor Upregulation Upon Endothelin-B Receptor Deficiency: A Neuroprotective Substitution Effect?. Neurochem Res 30, 1305–1309 (2005). https://doi.org/10.1007/s11064-005-8802-3

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  • DOI: https://doi.org/10.1007/s11064-005-8802-3

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