Researchers investigated the molecular effects ofLithium, valproate and lamotrigine treatment in induced pluripotent stem cell (iPSC)-derived neural precursor cells (NPCs) generated from three healthy controls, three affective disorder Li responsive patients and three Li non-treated patients after six hours and one week of exposure.
[Molecular Psychiatry]
7753456
{7753456:QF8WAMNE}
apa
50
1
162902
https://www.stemcellsciencenews.com/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3A%22zotpress-2655173ccdf2da24de92480a0e0afeaa%22%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22QF8WAMNE%22%2C%22library%22%3A%7B%22id%22%3A7753456%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Osete%20et%20al.%22%2C%22parsedDate%22%3A%222021-06-01%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EOsete%2C%20J.%20R.%2C%20Akkouh%2C%20I.%20A.%2C%20de%20Assis%2C%20D.%20R.%2C%20Szabo%2C%20A.%2C%20Frei%2C%20E.%2C%20Hughes%2C%20T.%2C%20Smeland%2C%20O.%20B.%2C%20Steen%2C%20N.%20E.%2C%20Andreassen%2C%20O.%20A.%2C%20%26amp%3B%20Djurovic%2C%20S.%20%282021%29.%20Lithium%20increases%20mitochondrial%20respiration%20in%20iPSC-derived%20neural%20precursor%20cells%20from%20lithium%20responders.%20%3Ci%3EMolecular%20Psychiatry%3C%5C%2Fi%3E%2C%201%26%23x2013%3B17.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41380-021-01164-4%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41380-021-01164-4%3C%5C%2Fa%3E%20%3Ca%20title%3D%27Cite%20in%20RIS%20Format%27%20class%3D%27zp-CiteRIS%27%20href%3D%27https%3A%5C%2F%5C%2Fwww.stemcellsciencenews.com%5C%2Fwp-content%5C%2Fplugins%5C%2Fzotpress%5C%2Flib%5C%2Frequest%5C%2Frequest.cite.php%3Fapi_user_id%3D7753456%26amp%3Bitem_key%3DQF8WAMNE%27%3ECite%3C%5C%2Fa%3E%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Lithium%20increases%20mitochondrial%20respiration%20in%20iPSC-derived%20neural%20precursor%20cells%20from%20lithium%20responders%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jordi%20Requena%22%2C%22lastName%22%3A%22Osete%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ibrahim%20A.%22%2C%22lastName%22%3A%22Akkouh%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Denis%20Reis%22%2C%22lastName%22%3A%22de%20Assis%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Attila%22%2C%22lastName%22%3A%22Szabo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Evgeniia%22%2C%22lastName%22%3A%22Frei%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Timothy%22%2C%22lastName%22%3A%22Hughes%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Olav%20B.%22%2C%22lastName%22%3A%22Smeland%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nils%20Eiel%22%2C%22lastName%22%3A%22Steen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ole%20A.%22%2C%22lastName%22%3A%22Andreassen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Srdjan%22%2C%22lastName%22%3A%22Djurovic%22%7D%5D%2C%22abstractNote%22%3A%22Lithium%20%28Li%29%2C%20valproate%20%28VPA%29%20and%20lamotrigine%20%28LTG%29%20are%20commonly%20used%20to%20treat%20bipolar%20disorder%20%28BD%29.%20While%20their%20clinical%20efficacy%20is%20well%20established%2C%20the%20mechanisms%20of%20action%20at%20the%20molecular%20level%20are%20still%20incompletely%20understood.%20Here%20we%20investigated%20the%20molecular%20effects%20of%20Li%2C%20LTG%20and%20VPA%20treatment%20in%20induced%20pluripotent%20stem%20cell%20%28iPSC%29-derived%20neural%20precursor%20cells%20%28NPCs%29%20generated%20from%203%20healthy%20controls%20%28CTRL%29%2C%203%20affective%20disorder%20Li%20responsive%20patients%20%28Li-R%29%20and%203%20Li%20non-treated%20patients%20%28Li-N%29%20after%206%5Cu2009h%20and%201%20week%20of%20exposure.%20Differential%20expression%20%28DE%29%20analysis%20after%206%5Cu2009h%20of%20treatment%20revealed%20a%20transcriptional%20signature%20that%20was%20associated%20with%20all%20three%20drugs%20and%20most%20significantly%20enriched%20for%20ribosome%20and%20oxidative%20phosphorylation%20%28OXPHOS%29%20pathways.%20In%20addition%20to%20the%20shared%20DE%20genes%2C%20we%20found%20that%20Li%20exposure%20was%20associated%20with%20554%20genes%20uniquely%20regulated%20in%20Li-R%20NPCs%20and%20enriched%20for%20spliceosome%2C%20OXPHOS%20and%20thermogenesis%20pathways.%20In-depth%20analysis%20of%20the%20treatment-associated%20transcripts%20uncovered%20a%20significant%20decrease%20in%20intron%20retention%20rate%2C%20suggesting%20that%20the%20beneficial%20influence%20of%20these%20drugs%20might%20partly%20be%20related%20to%20splicing.%20We%20examined%20the%20mitochondrial%20respiratory%20function%20of%20the%20NPCs%20by%20exploring%20the%20drugs%5Cu2019%20effects%20on%20oxygen%20consumption%20rate%20%28OCR%29%20and%20glycolytic%20rate%20%28ECAR%29.%20Li%20improved%20OCR%20levels%20only%20in%20Li-R%20NPCs%20by%20enhancing%20maximal%20respiration%20and%20reserve%20capacity%2C%20while%20VPA%20enhanced%20maximal%20respiration%20and%20reserve%20capacity%20in%20Li-N%20NPCs.%20Overall%2C%20our%20findings%20further%20support%20the%20involvement%20of%20mitochondrial%20functions%20in%20the%20molecular%20mechanisms%20of%20mood%20stabilizers%20and%20suggest%20novel%20mechanisms%20related%20to%20the%20spliceosome%2C%20which%20warrant%20further%20investigation.%22%2C%22date%22%3A%222021-06-01%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41380-021-01164-4%22%2C%22ISSN%22%3A%221476-5578%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41380-021-01164-4%22%2C%22deleted%22%3A1%2C%22collections%22%3A%5B%22TUURQW3H%22%5D%2C%22dateModified%22%3A%222021-06-01T21%3A21%3A07Z%22%7D%7D%5D%7D
Osete, J. R., Akkouh, I. A., de Assis, D. R., Szabo, A., Frei, E., Hughes, T., Smeland, O. B., Steen, N. E., Andreassen, O. A., & Djurovic, S. (2021). Lithium increases mitochondrial respiration in iPSC-derived neural precursor cells from lithium responders. Molecular Psychiatry, 1–17. https://doi.org/10.1038/s41380-021-01164-4 Cite
