title: 2-Methyl-6-(phenylethynyl)pyridine Hydrochloride Modulates Metabotropic Glutamate 5 Receptors Endogenously Expressed in Zebrafish Brain.
abstract: 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 mGlu5receptor antagonist, has been suggested for pharmacological treatment of AD. The aim of the present work was to quantify mGlu5receptors 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 mGlu5receptors in brain from male than in that from female zebrafish. However, a significant increase of mGlu5receptor 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 mGlu5receptors 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.
authors.affiliation: Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Medicina de Ciudad Real/Facultad de Ciencias y Tecnologías Químicas, Universidad de Castilla-La Mancha, Centro Regional de Investigaciones Biomédicas (CRIB) , Avenida Camilo José Cela 10, 13071 Ciudad Real, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Albasanz
authors.affiliation: Neuron Bio S.A. , 18016 Granada, Spain.
authors.forename: Soraya
authors.initials: S
authors.lastname: Santana
authors.affiliation: Neuron Bio S.A. , 18016 Granada, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Guzman-Sanchez
authors.affiliation: Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Medicina de Ciudad Real/Facultad de Ciencias y Tecnologías Químicas, Universidad de Castilla-La Mancha, Centro Regional de Investigaciones Biomédicas (CRIB) , Avenida Camilo José Cela 10, 13071 Ciudad Real, Spain.
authors.forename: David
authors.initials: D
authors.lastname: León
authors.affiliation: Neuron Bio S.A. , 18016 Granada, Spain.
authors.forename: Javier S
authors.initials: JS
authors.lastname: Burgos
authors.affiliation: Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Medicina de Ciudad Real/Facultad de Ciencias y Tecnologías Químicas, Universidad de Castilla-La Mancha, Centro Regional de Investigaciones Biomédicas (CRIB) , Avenida Camilo José Cela 10, 13071 Ciudad Real, Spain.
authors.forename: Mairena
authors.initials: M
authors.lastname: Martín
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology*; D011869:Radioligand Assay; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D012727:Sex Characteristics; D013550:Swimming / Q000502:physiology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D029961:Zebrafish Proteins; C121465:6-methyl-2-(phenylethynyl)pyridine
keywords: Danio rerio; MPEP; locomotion; mGlu5; up-regulation