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Published on: May 23, 2013
2-Methyl-6-(phenylethynyl)pyridine Hydrochloride Modulates Metabotropic Glutamate 5 Receptors Endogenously Expressed
José Luis Albasanz1, Soraya Santana2, Fernando Guzman-Sanchez2
1Departamento 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.
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.
Insights
Zebrafish brain exhibits metabotropic glutamate 5 receptors, with MPEP treatment increasing these receptors in males. This treatment also reduced locomotor activity specifically in male zebrafish, suggesting a gender-specific role.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- Zebrafish are valuable models for studying human central nervous system disorders like Alzheimer's disease (AD).
- Metabotropic glutamate 5 (mGlu5) receptors are implicated in AD pathogenesis and are potential therapeutic targets.
- MPEP, a selective mGlu5 receptor antagonist, has been proposed for AD treatment.
Purpose of the Study:
- To quantify mGlu5 receptors in zebrafish brains.
- To investigate the effects of MPEP treatment on mGlu5 receptor levels and locomotor behavior in zebrafish.
- To explore potential gender-specific responses to mGlu5 receptor modulation.
Main Methods:
- Radioligand binding assays were used to quantify mGlu5 receptor presence.
- Open field tests were conducted to assess locomotor behavior.
- Zebrafish brains were analyzed for mGlu5 receptor expression and modulation by MPEP.
Main Results:
- A slightly higher concentration of mGlu5 receptors was observed in male zebrafish brains compared to females.
- MPEP treatment significantly increased mGlu5 receptor levels in male zebrafish but not in females.
- Locomotor activity was significantly decreased in male zebrafish following MPEP treatment, indicating a gender-specific behavioral response.
Conclusions:
- Zebrafish possess functional mGlu5 receptors that can be modulated by MPEP in a gender-specific manner.
- mGlu5 receptors appear to play a role in regulating locomotor activity in zebrafish.
- Zebrafish serve as a suitable model for investigating mGlu receptor function in neurological conditions.
