PUBLICATION
2-Methyl-6-(phenylethynyl)pyridine Hydrochloride Modulates Metabotropic Glutamate 5 Receptors Endogenously Expressed in Zebrafish Brain
- Authors
- Albasanz, J.L., Santana, S., Guzman-Sanchez, F., León, D.A., Burgos, J.S., Martin, M.
- ID
- ZDB-PUB-160917-2
- Date
- 2016
- Source
- ACS Chemical Neuroscience 7(12): 1690-1697 (Journal)
- Registered Authors
- Burgos, Javier S.
- Keywords
- none
- MeSH Terms
-
- Animals
- Brain/drug effects*
- Brain/metabolism*
- Cell Membrane/drug effects
- Cell Membrane/metabolism
- Excitatory Amino Acid Antagonists/pharmacology*
- Female
- Male
- Motor Activity/drug effects
- Motor Activity/physiology
- Pyridines/pharmacology*
- Radioligand Assay
- Receptor, Metabotropic Glutamate 5/metabolism*
- Sex Characteristics
- Swimming/physiology
- Zebrafish
- Zebrafish Proteins/metabolism*
- PubMed
- 27635438 Full text @ ACS Chem. Neurosci.
Citation
Albasanz, J.L., Santana, S., Guzman-Sanchez, F., León, D.A., Burgos, J.S., Martin, M. (2016) 2-Methyl-6-(phenylethynyl)pyridine Hydrochloride Modulates Metabotropic Glutamate 5 Receptors Endogenously Expressed in Zebrafish Brain. ACS Chemical Neuroscience. 7(12):1690-1697.
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 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping