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mRNA Expression of SMPD1 Encoding Acid Sphingomyelinase Decreases upon Antidepressant Treatment.
Rhein, Cosima; Zoicas, Iulia; Marx, Lena M; Zeitler, Stefanie; Hepp, Tobias; von Zimmermann, Claudia; Mühle, Christiane; Richter-Schmidinger, Tanja; Lenz, Bernd; Erim, Yesim; Reichel, Martin; Gulbins, Erich; Kornhuber, Johannes.
Afiliación
  • Rhein C; Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 6, D-91054 Erlangen, Germany.
  • Zoicas I; Department of Psychosomatic Medicine and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), D-91054 Erlangen, Germany.
  • Marx LM; Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 6, D-91054 Erlangen, Germany.
  • Zeitler S; Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 6, D-91054 Erlangen, Germany.
  • Hepp T; Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 6, D-91054 Erlangen, Germany.
  • von Zimmermann C; Department of Psychosomatic Medicine and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), D-91054 Erlangen, Germany.
  • Mühle C; Institute of Medical Informatics, Biometry and Epidemiology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), D-91054 Erlangen, Germany.
  • Richter-Schmidinger T; Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 6, D-91054 Erlangen, Germany.
  • Lenz B; Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 6, D-91054 Erlangen, Germany.
  • Erim Y; Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 6, D-91054 Erlangen, Germany.
  • Reichel M; Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 6, D-91054 Erlangen, Germany.
  • Gulbins E; Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health (CIMH), Medical Faculty Mannheim, Heidelberg University, D-68159 Mannheim, Germany.
  • Kornhuber J; Department of Psychosomatic Medicine and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), D-91054 Erlangen, Germany.
Int J Mol Sci ; 22(11)2021 May 27.
Article en En | MEDLINE | ID: mdl-34071826
Major depressive disorder (MDD) is a severe psychiatric condition with key symptoms of low mood and lack of motivation, joy, and pleasure. Recently, the acid sphingomyelinase (ASM)/ceramide system has been implicated in the pathogenesis of MDD. ASM is a lysosomal glycoprotein that catalyzes the hydrolysis of sphingomyelin, an abundant component of membranes, into the bioactive sphingolipid ceramide, which impacts signaling pathways. ASM activity is inhibited by several common antidepressant drugs. Human and murine studies have confirmed that increased ASM activity and ceramide levels are correlated with MDD. To define a molecular marker for treatment monitoring, we investigated the mRNA expression of SMPD1, which encodes ASM, in primary cell culture models, a mouse study, and a human study with untreated MDD patients before and after antidepressive treatment. Our cell culture study showed that a common antidepressant inhibited ASM activity at the enzymatic level and also at the transcriptional level. In a genetically modified mouse line with depressive-like behavior, Smpd1 mRNA expression in dorsal hippocampal tissue was significantly decreased after treatment with a common antidepressant. The large human study showed that SMPD1 mRNA expression in untreated MDD patients decreased significantly after antidepressive treatment. This translational study shows that SMPD1 mRNA expression could serve as a molecular marker for treatment and adherence monitoring of MDD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esfingomielina Fosfodiesterasa / ARN Mensajero / Biomarcadores / Expresión Génica / Regulación de la Expresión Génica / Antidepresivos Tipo de estudio: Etiology_studies / Observational_studies Límite: Animals / Humans Idioma: En Revista: Int J Mol Sci Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esfingomielina Fosfodiesterasa / ARN Mensajero / Biomarcadores / Expresión Génica / Regulación de la Expresión Génica / Antidepresivos Tipo de estudio: Etiology_studies / Observational_studies Límite: Animals / Humans Idioma: En Revista: Int J Mol Sci Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza