Effects of memantine on mania-like phenotypes exhibited by Drosophila Shaker mutants.
Drosophila
Shaker channel
NMDA receptor
bipolar disorder
glutamate
memantine
Journal
CNS neuroscience & therapeutics
ISSN: 1755-5949
Titre abrégé: CNS Neurosci Ther
Pays: England
ID NLM: 101473265
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
revised:
17
02
2023
received:
16
11
2022
accepted:
19
02
2023
medline:
7
7
2023
pubmed:
22
3
2023
entrez:
21
3
2023
Statut:
ppublish
Résumé
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. 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. 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.
Identifiants
pubmed: 36942502
doi: 10.1111/cns.14145
pmc: PMC10324369
doi:
Substances chimiques
Memantine
W8O17SJF3T
Receptors, N-Methyl-D-Aspartate
0
Glutamic Acid
3KX376GY7L
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1750-1761Informations de copyright
© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.
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