Neutral sphingomyelinase mediates the co-morbidity trias of alcohol abuse, major depression and bone defects

  1. Kalinichenko, Liubov S.
  2. Mühle, Christiane ORCID logo
  3. Jia, Tianye
  4. Anderheiden, Felix
  5. Datz, Maria
  6. Eberle, Anna-Lisa ORCID logo
  7. Eulenburg, Volker
  8. Granzow, Jonas
  9. Hofer, Martin
  10. Hohenschild, Julia
  11. Huber, Sabine E.
  12. Kämpf, Stefanie
  13. Kogias, Georgios
  14. Lacatusu, Laura
  15. Lugmair, Charlotte
  16. Taku, Stephen Mbu
  17. Meixner, Doris
  18. Tesch, Nina
  19. Praetner, Marc
  20. Rhein, Cosima
  21. Sauer, Christina ORCID logo
  22. Scholz, Jessica
  23. Ulrich, Franziska
  24. Valenta, Florian
  25. Weigand, Esther
  26. Werner, Markus
  27. Tay, Nicole ORCID logo
  28. Mc Veigh, Conor J.
  29. Haase, Jana ORCID logo
  30. Wang, An-Li
  31. Abdel-Hafiz, Laila
  32. Huston, Joseph P.
  33. Smaga, Irena
  34. Frankowska, Małgorzata ORCID logo
  35. Filip, Malgorzata
  36. Lourdusamy, Anbarasu ORCID logo
  37. Kirchner, Philipp
  38. Ekici, Arif ORCID logo
  39. Marx, Lena M.
  40. Suresh, Neeraja Puliparambil
  41. Frischknecht, Renato
  42. Fejtova, Anna ORCID logo
  43. Saied, Essa M.
  44. Arenz, Christoph ORCID logo
  45. Bozec, Aline ORCID logo
  46. Wank, Isabel
  47. Kreitz, Silke
  48. Hess, Andreas
  49. Bäuerle, Tobias
  50. Ledesma, Maria Dolores ORCID logo
  51. Mitroi, Daniel N.
  52. Miranda, André M.
  53. Oliveira, Tiago G.
  54. Gulbins, Erich
  55. Lenz, Bernd ORCID logo
  56. Schumann, Gunter
  57. Kornhuber, Johannes ORCID logo
  58. Müller, Christian ORCID logo

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1000 Titel
  • Neutral sphingomyelinase mediates the co-morbidity trias of alcohol abuse, major depression and bone defects
1000 Autor/in
  1. Kalinichenko, Liubov S. |
  2. Mühle, Christiane |
  3. Jia, Tianye |
  4. Anderheiden, Felix |
  5. Datz, Maria |
  6. Eberle, Anna-Lisa |
  7. Eulenburg, Volker |
  8. Granzow, Jonas |
  9. Hofer, Martin |
  10. Hohenschild, Julia |
  11. Huber, Sabine E. |
  12. Kämpf, Stefanie |
  13. Kogias, Georgios |
  14. Lacatusu, Laura |
  15. Lugmair, Charlotte |
  16. Taku, Stephen Mbu |
  17. Meixner, Doris |
  18. Tesch, Nina |
  19. Praetner, Marc |
  20. Rhein, Cosima |
  21. Sauer, Christina |
  22. Scholz, Jessica |
  23. Ulrich, Franziska |
  24. Valenta, Florian |
  25. Weigand, Esther |
  26. Werner, Markus |
  27. Tay, Nicole |
  28. Mc Veigh, Conor J. |
  29. Haase, Jana |
  30. Wang, An-Li |
  31. Abdel-Hafiz, Laila |
  32. Huston, Joseph P. |
  33. Smaga, Irena |
  34. Frankowska, Małgorzata |
  35. Filip, Malgorzata |
  36. Lourdusamy, Anbarasu |
  37. Kirchner, Philipp |
  38. Ekici, Arif |
  39. Marx, Lena M. |
  40. Suresh, Neeraja Puliparambil |
  41. Frischknecht, Renato |
  42. Fejtova, Anna |
  43. Saied, Essa M. |
  44. Arenz, Christoph |
  45. Bozec, Aline |
  46. Wank, Isabel |
  47. Kreitz, Silke |
  48. Hess, Andreas |
  49. Bäuerle, Tobias |
  50. Ledesma, Maria Dolores |
  51. Mitroi, Daniel N. |
  52. Miranda, André M. |
  53. Oliveira, Tiago G. |
  54. Gulbins, Erich |
  55. Lenz, Bernd |
  56. Schumann, Gunter |
  57. Kornhuber, Johannes |
  58. Müller, Christian |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-09-28
1000 Erschienen in
1000 Quellenangabe
  • 26(12):7403-7416
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1038/s41380-021-01304-w |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8872992/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Mental disorders are highly comorbid and occur together with physical diseases, which are often considered to arise from separate pathogenic pathways. We observed in alcohol-dependent patients increased serum activity of neutral sphingomyelinase. A genetic association analysis in 456,693 volunteers found associations of haplotypes of SMPD3 coding for NSM-2 (NSM) with alcohol consumption, but also with affective state, and bone mineralisation. Functional analysis in mice showed that NSM controls alcohol consumption, affective behaviour, and their interaction by regulating hippocampal volume, cortical connectivity, and monoaminergic responses. Furthermore, NSM controlled bone-brain communication by enhancing osteocalcin signalling, which can independently supress alcohol consumption and reduce depressive behaviour. Altogether, we identified a single gene source for multiple pathways originating in the brain and bone, which interlink disorders of a mental-physical co-morbidity trias of alcohol abuse-depression/anxiety-bone disorder. Targeting NSM and osteocalcin signalling may, thus, provide a new systems approach in the treatment of a mental-physical co-morbidity trias.
1000 Sacherschließung
lokal Mice [MeSH]
lokal Article
lokal Sphingomyelin Phosphodiesterase/genetics [MeSH]
lokal Neuroscience
lokal Alcoholism/genetics [MeSH]
lokal Morbidity [MeSH]
lokal Humans [MeSH]
lokal Comorbidity [MeSH]
lokal Depressive Disorder, Major/genetics [MeSH]
lokal Animals [MeSH]
lokal Addiction
lokal Bone Diseases/genetics [MeSH]
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/S2FsaW5pY2hlbmtvLCBMaXVib3YgUy4=|https://orcid.org/0000-0001-7517-9154|https://frl.publisso.de/adhoc/uri/SmlhLCBUaWFueWU=|https://frl.publisso.de/adhoc/uri/QW5kZXJoZWlkZW4sIEZlbGl4|https://frl.publisso.de/adhoc/uri/RGF0eiwgTWFyaWE=|https://orcid.org/0000-0001-6657-5796|https://frl.publisso.de/adhoc/uri/RXVsZW5idXJnLCBWb2xrZXI=|https://frl.publisso.de/adhoc/uri/R3JhbnpvdywgSm9uYXM=|https://frl.publisso.de/adhoc/uri/SG9mZXIsIE1hcnRpbg==|https://frl.publisso.de/adhoc/uri/SG9oZW5zY2hpbGQsIEp1bGlh|https://frl.publisso.de/adhoc/uri/SHViZXIsIFNhYmluZSBFLg==|https://frl.publisso.de/adhoc/uri/S8OkbXBmLCBTdGVmYW5pZQ==|https://frl.publisso.de/adhoc/uri/S29naWFzLCBHZW9yZ2lvcw==|https://frl.publisso.de/adhoc/uri/TGFjYXR1c3UsIExhdXJh|https://frl.publisso.de/adhoc/uri/THVnbWFpciwgQ2hhcmxvdHRl|https://frl.publisso.de/adhoc/uri/VGFrdSwgU3RlcGhlbiBNYnU=|https://frl.publisso.de/adhoc/uri/TWVpeG5lciwgRG9yaXM=|https://frl.publisso.de/adhoc/uri/VGVzY2gsIE5pbmE=|https://frl.publisso.de/adhoc/uri/UHJhZXRuZXIsIE1hcmM=|https://frl.publisso.de/adhoc/uri/UmhlaW4sIENvc2ltYQ==|https://orcid.org/0000-0002-5073-9693|https://frl.publisso.de/adhoc/uri/U2Nob2x6LCBKZXNzaWNh|https://frl.publisso.de/adhoc/uri/VWxyaWNoLCBGcmFuemlza2E=|https://frl.publisso.de/adhoc/uri/VmFsZW50YSwgRmxvcmlhbg==|https://frl.publisso.de/adhoc/uri/V2VpZ2FuZCwgRXN0aGVy|https://frl.publisso.de/adhoc/uri/V2VybmVyLCBNYXJrdXM=|https://orcid.org/0000-0002-1307-408X|https://frl.publisso.de/adhoc/uri/TWMgVmVpZ2gsIENvbm9yIEou|https://orcid.org/0000-0002-5949-8355|https://frl.publisso.de/adhoc/uri/V2FuZywgQW4tTGk=|https://frl.publisso.de/adhoc/uri/QWJkZWwtSGFmaXosIExhaWxh|https://frl.publisso.de/adhoc/uri/SHVzdG9uLCBKb3NlcGggUC4=|https://frl.publisso.de/adhoc/uri/U21hZ2EsIElyZW5h|https://orcid.org/0000-0002-6646-6140|https://frl.publisso.de/adhoc/uri/RmlsaXAsIE1hbGdvcnphdGE=|https://orcid.org/0000-0002-1978-6301|https://frl.publisso.de/adhoc/uri/S2lyY2huZXIsIFBoaWxpcHA=|https://orcid.org/0000-0001-6099-7066|https://frl.publisso.de/adhoc/uri/TWFyeCwgTGVuYSBNLg==|https://frl.publisso.de/adhoc/uri/U3VyZXNoLCBOZWVyYWphIFB1bGlwYXJhbWJpbA==|https://frl.publisso.de/adhoc/uri/RnJpc2Noa25lY2h0LCBSZW5hdG8=|https://orcid.org/0000-0002-1815-4409|https://frl.publisso.de/adhoc/uri/U2FpZWQsIEVzc2EgTS4=|https://orcid.org/0000-0001-7613-9437|https://orcid.org/0000-0001-8174-2118|https://frl.publisso.de/adhoc/uri/V2FuaywgSXNhYmVs|https://frl.publisso.de/adhoc/uri/S3JlaXR6LCBTaWxrZQ==|https://frl.publisso.de/adhoc/uri/SGVzcywgQW5kcmVhcw==|https://frl.publisso.de/adhoc/uri/QsOkdWVybGUsIFRvYmlhcw==|https://orcid.org/0000-0002-5679-6891|https://frl.publisso.de/adhoc/uri/TWl0cm9pLCBEYW5pZWwgTi4=|https://frl.publisso.de/adhoc/uri/TWlyYW5kYSwgQW5kcsOpIE0u|https://frl.publisso.de/adhoc/uri/T2xpdmVpcmEsIFRpYWdvIEcu|https://frl.publisso.de/adhoc/uri/R3VsYmlucywgRXJpY2g=|https://orcid.org/0000-0001-6086-0924|https://frl.publisso.de/adhoc/uri/U2NodW1hbm4sIEd1bnRlcg==|https://orcid.org/0000-0002-8096-3987|https://orcid.org/0000-0002-5325-9900
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