2-Methyl-6-(phenylethynyl)pyridine Hydrochloride Modulates Metabotropic Glutamate 5 Receptors Endogenously Expressed in Zebrafish Brain

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• 作者：José Luis Albasanz ; Soraya Santana ; Fernando Guzman-Sanchez ; David León ; Javier S. Burgos ; Mairena Martín
• 刊名：ACS Chemical Neuroscience
• 出版年：2016
• 出版时间：December 21, 2016
• 年：2016
• 卷：7
• 期：12
• 页码：1690-1697
• 全文大小：400K
• ISSN：1948-7193

文摘

Due to phylogenetic proximity to the human, zebrafish has been recognized as a reliable model to study Alzheimer’s disease (AD) and other central nervous system disorders. Furthermore, metabotropic glutamate receptors have been previously reported to be impaired in brain from AD patients. Metabotropic glutamate 5 (mGlu₅) receptors are G-protein coupled receptors proposed as potential targets for therapy of different neurodegenerative disorders. Thus, MPEP (2-methyl-6-(phenylethynyl)pyridine hydrochloride), a selective noncompetitive mGlu₅ receptor antagonist, has been suggested for pharmacological treatment of AD. The aim of the present work was to quantify mGlu₅ receptors in brain from zebrafish and to study the possible modulation of these receptors by MPEP treatment. To this end, radioligand binding assay and open field test were used. Results showed a slightly higher presence of mGlu₅ receptors in brain from male than in that from female zebrafish. However, a significant increase of mGlu₅ receptor in male without variation in female was observed after MPEP treatment. This gender specific response was also observed in locomotor behavior, being significantly decreased only in male zebrafish. These results confirm the presence of mGlu₅ receptors in brain from zebrafish and their gender specific modulation by selective antagonist treatment and suggest a role of these receptors on locomotor activity, which is affected in many disorders. In addition, our data point to zebrafish as a useful model to study mGlu receptor function in both healthy and pathological conditions.