title: Mgat5 modulates the effect of early life stress on adult behavior and physical health in mice.
abstract: Psychosocial adversity in early life increases the likelihood of mental and physical illness, but the underlying mechanisms are poorly understood. Mgat5 is an N-acetylglucosaminyltransferase in the Golgi pathway that remodels the N-glycans of glycoproteins at the cell surface. Mice lacking Mgat5 display conditional phenotypes in behaviour, immunity, metabolism, aging and cancer susceptibility. Here we investigated potential gene-environment interactions between Mgat5 and early life adversity on behaviour and physiological measures of physical health. Mgat5(-/-) mutant and Mgat5(+/+) wild-type C57Bl/6 littermates were subject to maternal separation or foster rearing as an early life stressor, in comparison to control mice reared normally. We found an interaction between Mgat5 genotype and maternal rearing condition in which Mgat5(-/-) mice subjected to early life stress had lower glucose levels and higher bone density. Mgat5(-/-) genotype was also associated with less immobility in the forced swim test and greater sucrose consumption, consistent with a less depression-like phenotype. Cortical neuron dendrite spine density and branching was altered by Mgat5 deletion as well. In general, Mgat5 genotype affects both behaviour and physical outcomes in response to early life stress, suggesting some shared pathways for both in this model. These results provide a starting point for studying the mechanisms by which protein N-glycosylation mediates the effects of early life adversity.
authors.affiliation: Institute of Medical Science, University of Toronto, Medical Sciences Building, 1 King's College Circle, Room 2374, Toronto, Ontario, M5S 1A8, Canada; Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada.
authors.forename: Laura
authors.initials: L
authors.lastname: Feldcamp
authors.affiliation: Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada.
authors.forename: Jean-Sebastien
authors.initials: JS
authors.lastname: Doucet
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, Ontario, M5G 1X5, Canada.
authors.forename: Judy
authors.initials: J
authors.lastname: Pawling
authors.affiliation: Ontario Shores Centre for Mental Health Sciences, 700 Gordon St, Whitby, Ontario, Canada; Department of Psychiatry, University of Toronto, 250 College Street, 8th Floor, Toronto, Ontario, M5T 1R8, Canada.
authors.forename: Marc P
authors.initials: MP
authors.lastname: Fadel
authors.affiliation: Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fletcher
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, Ontario, M5G 1X5, Canada; Department of Psychiatry, University of Toronto, 250 College Street, 8th Floor, Toronto, Ontario, M5T 1R8, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Maunder
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, Ontario, M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Medical Sciences Building, Room 4386, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada; Department of Laboratory Medicine and Pathology, University of Toronto, Medical Sciences Building, 1 King's College Circle, 6th Floor, Toronto, Ontario, M5S 1A8, Canada.
authors.forename: James W
authors.initials: JW
authors.lastname: Dennis
authors.affiliation: Institute of Medical Science, University of Toronto, Medical Sciences Building, 1 King's College Circle, Room 2374, Toronto, Ontario, M5S 1A8, Canada; Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada; Department of Psychiatry, University of Toronto, 250 College Street, 8th Floor, Toronto, Ontario, M5T 1R8, Canada; Department of Pharmacology, University of Toronto, Medical Sciences Building, Rm 4207, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada,. Electronic address: albert.wong@utoronto.ca.
authors.forename: Albert H C
authors.initials: AH
authors.lastname: Wong
mesh_terms: D000818:Animals; D001835:Body Weight; D015519:Bone Density; D001921:Brain / Q000473:pathology; D003345:Corticosterone / Q000097:blood; D049229:Dendritic Spines / Q000473:pathology; D003863:Depression / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D059647:Gene-Environment Interaction; D005947:Glucose / Q000378:metabolism; D008297:Male; D008425:Maternal Behavior; D008426:Maternal Deprivation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000473:pathology; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology*
chemical_list: D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase; D005947:Glucose; D003345:Corticosterone
keywords: Bone density; Corticosterone; Early life adversity; Mgat5; Neuron spine density