title: Social defeat leads to changes in the endocannabinoid system: An overexpression of calreticulin and motor impairment in mice.
abstract: Prolonged and sustained stimulation of the hypothalamo-pituitary-adrenal axis have adverse effects on numerous brain regions, including the cerebellum. Motor coordination and motor learning are essential for animal and require the regulation of cerebellar neurons. The G-protein-coupled cannabinoid CB1 receptor coordinates synaptic transmission throughout the CNS and is of highest abundance in the cerebellum. Accordingly, the aim of this study was to investigate the long-lasting effects of chronic psychosocial stress on motor coordination and motor learning, CB1 receptor expression, endogenous cannabinoid ligands and gene expression in the cerebellum. After chronic psychosocial stress, motor coordination and motor learning were impaired as indicated the righting reflex and the rota-rod. The amount of the endocannabinoid 2-AG increased while CB1 mRNA and protein expression were downregulated after chronic stress. Transcriptome analysis revealed 319 genes differentially expressed by chronic psychosocial stress in the cerebellum; mainly involved in synaptic transmission, transmission of nerve impulse, and cell-cell signaling. Calreticulin was validated as a stress candidate gene. The present study provides evidence that chronic stress activates calreticulin and might be one of the pathological mechanisms underlying the motor coordination and motor learning dysfunctions seen in social defeat mice.
authors.affiliation: Dept. of Psychiatry and Psychotherapy, University of Göttingen, Germany; Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany. Electronic address: jordi.tomas-roig@med.uni-goettingen.de.
authors.forename: J
authors.initials: J
authors.lastname: Tomas-Roig
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Piscitelli
authors.affiliation: Institute for Bioengineering of Catalonia (IBEC), Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), and Dept. of Cell Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Gil
authors.affiliation: Institute for Bioengineering of Catalonia (IBEC), Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), and Dept. of Cell Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Del Río
authors.affiliation: Dept. of Psychiatry and Psychotherapy, University of Göttingen, Germany; Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
authors.forename: T P
authors.initials: TP
authors.lastname: Moore
authors.affiliation: Laboratory for Aging and Cognitive Diseases, European Neuroscience Institute, Göttingen, Germany; University of Health and Allied Sciences, Ho, Ghana.
authors.forename: H
authors.initials: H
authors.lastname: Agbemenyah
authors.affiliation: Dept. of Developmental Biochemistry, Göttingen, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Salinas-Riester
authors.affiliation: Dept. of Developmental Biochemistry, Göttingen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Pommerenke
authors.affiliation: Dept. of Medical Statistics, University Medical Center, Göttingen, Germany; Dept. of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Lorenzen
authors.affiliation: Dept. of Medical Statistics, University Medical Center, Göttingen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Beißbarth
authors.affiliation: Johann-Friedrich-Blumenbach Institute for Zoology and Anthropology, Developmental Biology, Göttingen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Hoyer-Fender
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Di Marzo
authors.affiliation: Dept. of Psychiatry and Psychotherapy, University of Göttingen, Germany; Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Havemann-Reinecke
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D037282:Calreticulin / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D063388:Endocannabinoids / Q000378:metabolism*; D020869:Gene Expression Profiling; D005989:Glycerides / Q000378:metabolism; D007858:Learning / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D011597:Psychomotor Performance / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D045442:Rotarod Performance Test; D012919:Social Behavior; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D037282:Calreticulin; D063388:Endocannabinoids; D005989:Glycerides; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; C094503:glyceryl 2-arachidonate
keywords: Behavior; Calreticulin; Cerebellum; Endocannabinoid system; Psychosocial stress; RNA seq.