Artykuł w czasopiśmie
Brak miniatury
Licencja
TCF7L2 mediates the cellular and behavioral response to chronic lithium treatment in animal models
| cris.lastimport.scopus | 2024-02-12T20:21:37Z |
| dc.abstract.pl | The mechanism of lithium's therapeutic action remains obscure, hindering the discovery of safer treatments for bipolar disorder. Lithium can act as an inhibitor of the kinase GSK3α/β, which in turn negatively regulates β-catenin, a co-activator of LEF1/TCF transcription factors. However, unclear is whether therapeutic levels of lithium activate β-catenin in the brain, and whether this activation could have a therapeutic significance. To address this issue we chronically treated mice with lithium. Although the level of non-phospho-β-catenin increased in all of the brain areas examined, β-catenin translocated into cellular nuclei only in the thalamus. Similar results were obtained when thalamic and cortical neurons were treated with a therapeutically relevant concentration of lithium in vitro. We tested if TCF7L2, a member of LEF1/TCF family that is highly expressed in the thalamus, facilitated the activation of β-catenin. Silencing of Tcf7l2 in thalamic neurons prevented β-catenin from entering the nucleus, even when the cells were treated with lithium. Conversely, when Tcf7l2 was ectopically expressed in cortical neurons, β-catenin shifted to the nucleus, and lithium augmented this process. Lastly, we silenced tcf7l2 in zebrafish and exposed them to lithium for 3 days, to evaluate whether TCF7L2 is involved in the behavioral response. Lithium decreased the dark-induced activity of control zebrafish, whereas the activity of zebrafish with tcf7l2 knockdown was unaltered. We conclude that therapeutic levels of lithium activate β-catenin selectively in thalamic neurons. This effect is determined by the presence of TCF7L2, and potentially contributes to the therapeutic response. |
| dc.affiliation | Uniwersytet Warszawski |
| dc.contributor.author | Brożko, Nikola |
| dc.contributor.author | Misztal, Katarzyna |
| dc.contributor.author | Kuźnicki, Jacek |
| dc.contributor.author | Wiśniewska, Marta |
| dc.contributor.author | Brzozowska, Katarzyna |
| dc.contributor.author | Szewczyk, Łukasz |
| dc.contributor.author | Nagalski, Andrzej |
| dc.contributor.author | Jankowska, Marta |
| dc.date.accessioned | 2024-01-26T09:41:51Z |
| dc.date.available | 2024-01-26T09:41:51Z |
| dc.date.issued | 2017 |
| dc.description.finance | Nie dotyczy |
| dc.description.version | FINAL_PUBLISHED |
| dc.identifier.doi | 10.1016/J.NEUROPHARM.2016.10.027 |
| dc.identifier.issn | 0028-3908 |
| dc.identifier.uri | https://repozytorium.uw.edu.pl//handle/item/121575 |
| dc.pbn.affiliation | biological sciences |
| dc.relation.ispartof | Neuropharmacology |
| dc.rights | Other |
| dc.sciencecloud | nosend |
| dc.subject.en | Behavior |
| dc.subject.en | Bipolar disorder |
| dc.subject.en | Lithium treatment |
| dc.subject.en | TCF7L2 |
| dc.subject.en | Wnt signaling |
| dc.subject.en | β-catenin |
| dc.title | TCF7L2 mediates the cellular and behavioral response to chronic lithium treatment in animal models |
| dc.type | JournalArticle |
| dspace.entity.type | Publication |