% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Gttert:163462,
      author       = {Göttert, Ria and Fidzinski, Pawel and Kraus, Larissa and
                      Schneider, Ulf Christoph and Holtkamp, Martin and Endres,
                      Matthias and Gertz, Karen and Kronenberg, Golo},
      title        = {{L}ithium inhibits tryptophan catabolism via the
                      inflammation-induced kynurenine pathway in human microglia.},
      journal      = {Glia},
      volume       = {70},
      number       = {3},
      issn         = {1098-1136},
      address      = {Bognor Regis [u.a.]},
      publisher    = {Wiley-Liss},
      reportid     = {DZNE-2022-00222},
      pages        = {558 - 571},
      year         = {2022},
      note         = {(CC BY-NC)},
      abstract     = {Despite its decades' long therapeutic use in psychiatry,
                      the biological mechanisms underlying lithium's
                      mood-stabilizing effects have remained largely elusive.
                      Here, we investigated the effect of lithium on tryptophan
                      breakdown via the kynurenine pathway using immortalized
                      human microglia cells, primary human microglia isolated from
                      surgical specimens, and microglia-like cells differentiated
                      from human induced pluripotent stem cells. Interferon
                      (IFN)-γ, but not lipopolysaccharide, was able to activate
                      immortalized human microglia, inducing a robust increase in
                      indoleamine-2,3-dioxygenase (IDO1) mRNA transcription, IDO1
                      protein expression, and activity. Further, chromatin
                      immunoprecipitation verified enriched binding of both STAT1
                      and STAT3 to the IDO1 promoter. Lithium counteracted these
                      effects, increasing inhibitory GSK3βS9 phosphorylation and
                      reducing STAT1S727 and STAT3Y705 phosphorylation levels in
                      IFN-γ treated cells. Studies in primary human microglia and
                      hiPSC-derived microglia confirmed the anti-inflammatory
                      effects of lithium, highlighting that IDO activity is
                      reduced by GSK3 inhibitor SB-216763 and STAT inhibitor
                      nifuroxazide via downregulation of P-STAT1S727 and
                      P-STAT3Y705 . Primary human microglia differed from
                      immortalized human microglia and hiPSC derived
                      microglia-like cells in their strong sensitivity to LPS,
                      resulting in robust upregulation of IDO1 and
                      anti-inflammatory cytokine IL-10. While lithium again
                      decreased IDO1 activity in primary cells, it further
                      increased release of IL-10 in response to LPS. Taken
                      together, our study demonstrates that lithium inhibits the
                      inflammatory kynurenine pathway in the microglia compartment
                      of the human brain.},
      keywords     = {Glycogen Synthase Kinase 3: metabolism / Glycogen Synthase
                      Kinase 3: pharmacology / Humans / Indoleamine-Pyrrole
                      2,3,-Dioxygenase: genetics / Indoleamine-Pyrrole
                      2,3,-Dioxygenase: metabolism / Indoleamine-Pyrrole
                      2,3,-Dioxygenase: pharmacology / Induced Pluripotent Stem
                      Cells: metabolism / Inflammation: metabolism / Kynurenine:
                      metabolism / Kynurenine: pharmacology / Lithium: metabolism
                      / Lithium: pharmacology / Microglia: metabolism /
                      Tryptophan: metabolism / Tryptophan: pharmacology /
                      depression (Other) / kynurenine (Other) / lithium (Other) /
                      microglia (Other) / tryptophan (Other) / Indoleamine-Pyrrole
                      2,3,-Dioxygenase (NLM Chemicals) / Kynurenine (NLM
                      Chemicals) / Tryptophan (NLM Chemicals) / Lithium (NLM
                      Chemicals) / Glycogen Synthase Kinase 3 (NLM Chemicals)},
      cin          = {AG Endres},
      ddc          = {610},
      cid          = {I:(DE-2719)1811005},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34862988},
      doi          = {10.1002/glia.24123},
      url          = {https://pub.dzne.de/record/163462},
}