Chronic lithium treatment alters NMDA and AMPA receptor synaptic availability and dendritic spine organization in the rat hippocampus

Background: The mechanisms underlying the action of lithium (LiCl) in bipolar disorder - (BD) are still far from being completely understood. Previous evidence has revealed that BD is characterized - by glutamate hyperexcitability, suggesting that LiCl may act, at least partially, by toning down - g...

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Hauptverfasser: Caffino, Lucia (VerfasserIn) , Targa, Giorgia (VerfasserIn) , Mallien, Anne Stephanie (VerfasserIn) , Mottarlini, Francesca (VerfasserIn) , Rizzi, Beatrice (VerfasserIn) , Homberg, Judith R. (VerfasserIn) , Gass, Peter (VerfasserIn) , Fumagalli, Fabio (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2024
In: Current neuropharmacology
Year: 2024, Jahrgang: 22, Heft: 12, Pages: 2045-2058
ISSN:1875-6190
DOI:10.2174/1570159X21666230913144420
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.2174/1570159X21666230913144420
Verlag, kostenfrei, Volltext: http://www.eurekaselect.com/article/134503
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Verfasserangaben:Lucia Caffino, Giorgia Targa, Anne Stephanie Mallien, Francesca Mottarlini, Beatrice Rizzi, Judith R. Homberg, Peter Gass and Fabio Fumagalli

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520 |a Background: The mechanisms underlying the action of lithium (LiCl) in bipolar disorder - (BD) are still far from being completely understood. Previous evidence has revealed that BD is characterized - by glutamate hyperexcitability, suggesting that LiCl may act, at least partially, by toning down - glutamatergic signaling abnormalities. - - - Objective: In this study, taking advantage of western blot and confocal microscopy, we used a combination - of integrative molecular and morphological approaches in rats exposed to repeated administration - of LiCl at a therapeutic dose (between 0.6 and 1.2 mmol/l) and sacrificed at two different time - points, i.e., 24 hours and 7 days after the last exposure. - - - Results: We report that repeated LiCl treatment activates multiple, parallel, but also converging forms - of compensatory neuroplasticity related to glutamatergic signaling. More specifically, LiCl promoted a - wave of neuroplasticity in the hippocampus, involving the synaptic recruitment of GluN2A-containing - NMDA receptors, GluA1-containing AMPA receptors, and the neurotrophin BDNF that are indicative - of a more plastic spine. The latter is evidenced by morphological analyses showing changes in dendritic - spine morphology, such as increased length and head diameter of such spines. These changes may - counteract the potentially negative extra-synaptic movements of GluN2B-containing NMDA receptors - as well as the increase in the formation of GluA2-lacking Ca2+-permeable AMPA receptors. - - - Conclusion: Our findings highlight a previously unknown cohesive picture of the glutamatergic implications - of LiCl action that persist long after the end of its administration, revealing for the first time - a profound and persistent reorganization of the glutamatergic postsynaptic density receptor composition - and structure. 
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700 1 |a Fumagalli, Fabio  |e VerfasserIn  |4 aut 
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