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

ABSTRACT: 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 redu

SUBMITTER: Kalinichenko LS 

PROVIDER: S-EPMC8872992 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature