Altered mannose metabolism in chronic stress and depression is rapidly reversed by vitamin B12

Patricia Franzka; Gustavo Turecki; Susana Cubillos; Takfarinas Kentache; Johann Steiner; Martin Walter; Christian A Hübner; Olivia Engmann

doi:10.3389/fnut.2022.981511

Altered mannose metabolism in chronic stress and depression is rapidly reversed by vitamin B12

Front Nutr. 2022 Oct 13:9:981511. doi: 10.3389/fnut.2022.981511. eCollection 2022.

Authors

Patricia Franzka¹, Gustavo Turecki², Susana Cubillos³, Takfarinas Kentache⁴, Johann Steiner⁵, Martin Walter⁶, Christian A Hübner¹, Olivia Engmann^{1

3}

Affiliations

¹ Institute of Human Genetics, University Hospital Jena, Friedrich Schiller University, Jena, Germany.
² Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
³ Institute for Biochemistry and Biophysics, Friedrich-Schiller-University Jena, Jena, Germany.
⁴ Laboratory of Physiological Chemistry, de Duve Institute, Brussels, Belgium.
⁵ Clinic for Psychiatry and Psychotherapy, University Hospital of Otto-von-Guericke-Universität Magdeburg, Magdeburg, Germany.
⁶ Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.

Abstract

GDP-Mannose Pyrophosphorylase B (GMPPB) is a key enzyme for glycosylation. Previous studies suggested a dysregulation of GMPBB and mannose in depression. Evidence, however, was sporadic and interventions to reverse these changes are unknown. Here, we show that GMPPB protein, but not RNA abundance is increased in the postmortem prefrontal cortex (PFC) of depressed patients and the chronic variable stress (CVS) mouse-model. This is accompanied by higher plasma mannose levels. Importantly, a single dose of intraperitoneally administered vitamin B12, which has previously been shown to rapidly reverse behavioral symptoms and molecular signatures of chronic stress in mice, normalized GMPPB plasma mannose levels and elevated GDP-mannose abundance. In summary, these data underline metabolic dysregulation in chronic stress and depression and provide further support for rapid effects of vitamin B12 on chronic stress.

Keywords: depression; glycosylation; mannose; stress; vitamin B12.