Effects of memantine on mania-like phenotypes exhibited by Drosophila Shaker mutants |
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| Authors: | Ignazia Mocci Maria Antonietta Casu Valeria Sogos Anna Liscia Rossella Angius Francesca Cadeddu Maura Fanti Patrizia Muroni Giuseppe Talani Andrea Diana Maria Collu Maria Dolores Setzu |
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| Affiliation: | 1. Institute of Translational Pharmacology, National Research Council, Science and Technology Park of Sardinia, Cagliari, Italy;2. Department of Biomedical Sciences, University of Cagliari, Monserrato, Italy;3. Unit of Biomedical Research Support, NMR Laboratory and Bioanalytical Technologies, Sardegna Ricerche, Science and Technology Park of Sardinia, Cagliari, Italy;4. Institute of Neuroscience, National Research Council, Monserrato, Italy;5. Department of Biomedical Sciences, University of Cagliari, Monserrato, Italy This work is dedicated to the memory of our dear friend and colleague Maria Collu. |
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| Abstract: | Introduction Increased glutamate levels and electrolytic fluctuations have been observed in acutely manic patients. Despite some efficacy of the non-competitive NMDA receptor antagonist memantine (Mem), such as antidepressant-like and mood-stabilizer drugs in clinical studies, its specific mechanisms of action are still uncertain. The present study aims to better characterize the Drosophila melanogaster fly Shaker mutants (SH), as a translational model of manic episodes within bipolar disorder in humans, and to investigate the potential anti-manic properties of Mem. Methods and Results Our findings showed typical behavioral abnormalities in SH, which mirrored with the overexpression of NMDAR-NR1 protein subunit, matched well to glutamate up-regulation. Such molecular features were associated to a significant reduction of SH brain volume in comparison to Wild Type strain flies (WT). Here we report on the ability of Mem treatment to ameliorate behavioral aberrations of SH (similar to that of Lithium), and its ability to reduce NMDAR-NR1 over-expression. Conclusions Our results show the involvement of the glutamatergic system in the SH, given the interaction between the Shaker channel and the NMDA receptor, suggesting this model as a promising tool for studying the neurobiology of bipolar disorders. Moreover, our results show Mem as a potential disease-modifying therapy, providing insight on new mechanisms of action. |
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| Keywords: | bipolar disorder Drosophila glutamate memantine NMDA receptor Shaker channel |
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