Olfactory stem cells reveal MOCOS as a new player in autism spectrum disorders

• DOI: 10.1038/mp.2015.106
• Publication Date: 2015-08-04T11:38:29Z
• Authors: F Féron; B Gepner; E Lacassagne; D Stephan; B Mesnage; M-P Blanchard; N Boulanger; C Tardif; A Devèze; S Rousseau; K Suzuki; J C Izpisua Belmonte; M Khrestchatisky; E Nivet; M Erard-Garcia
• Keywords: Adult; Male; 571; Autism Spectrum Disorder; autism spectrum disorders; [SHS.PSY]Humanities and Social Sciences/Psychology; MOCOS; Olfactory Receptor Neurons; [SHS.PSY] Humanities and Social Sciences/Psychology; Mice; 03 medical and health sciences; Olfactory Mucosa; stem cells; Animals; Humans; neurotransmission; [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]; Caenorhabditis elegans; 0303 health sciences; Stem Cells; 3. Good health; Mice, Inbred C57BL; autism spectrum disorders, neurotransmission , MOCOS, stem cells; Sulfurtransferases; [SCCO.PSYC]Cognitive science/Psychology; [SCCO.PSYC] Cognitive science/Psychology; [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]; Original Article; Female; France

With an onset under the age of 3 years, autism spectrum disorders (ASDs) are now understood as diseases arising from pre- and/or early postnatal brain developmental anomalies insults. To unveil molecular mechanisms taking place during misshaping developing brain, we chose to study cells that representative very stages ontogenesis, namely stem cells. Here report on MOlybdenum COfactor Sulfurase (MOCOS), enzyme involved in purine metabolism, a newly identified player ASD. We found adult nasal olfactory 11 adults with ASD MOCOS is downregulated most them when compared age- and gender-matched control without any neuropsychiatric disorders. Genetic approaches using vivo vitro engineered models converge indicate altered expression results neurotransmission synaptic defects. Furthermore, misexpression induces increased oxidative-stress sensitivity. Our demonstrate likely have impact neurodevelopment neurotransmission, may explain comorbid conditions, including gastrointestinal anticipate our discovery be fresh starting point for roles development its functional implications clinical symptoms. Moreover, suggests possible new diagnostic tests based expression, paves way drug screening targeting metabolism ultimately develop novel treatments