Tomas-Roig, J.a b , Piscitelli, F.c , Gil, V.d ,
del Río, J.A.d , Moore, T.P.a
b , Agbemenyah, H.e f
, Salinas-Riester, G.g , Pommerenke, C.g , Lorenzen, S.h i , Beißbarth, T.h ,
Hoyer-Fender, S.j , Di Marzo, V.c , Havemann-Reinecke, U.a b
Social defeat leads to changes
in the endocannabinoid system: An overexpression of calreticulin and motor impairment
in mice
(2016) Behavioural
Brain Research, 303, pp. 34-43.
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84956538557&partnerID=40&md5=b1f951427e42ed462e063faff10a2672
DOI: 10.1016/j.bbr.2016.01.036
AFFILIATIONS:
a) Dept. of Psychiatry and Psychotherapy, University of
Göttingen, Germany;
b) Center Nanoscale Microscopy and Molecular Physiology
of the Brain (CNMPB), Göttingen, Germany;
c)
Endocannabinoid Research Group,
Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche,
Pozzuoli, Italy;
d) Institute for Bioengineering of Catalonia (IBEC),
Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas
(CIBERNED), Dept. of Cell Biology, Faculty of Biology, University of Barcelona,
Barcelona, Spain;
e) Laboratory for Aging and Cognitive Diseases, European
Neuroscience Institute, Göttingen, Germany;
f) University of Health and Allied Sciences, Ho, Ghana;
g) Dept. of Developmental Biochemistry, Göttingen,
Germany;
h) Dept. of Medical Statistics, University Medical
Center, Göttingen, Germany;
i)
Dept. of Molecular
Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany;
j)
Johann-Friedrich-Blumenbach
Institute for Zoology and Anthropology, Developmental Biology, Göttingen,
Germany
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. © 2016 Elsevier B.V.
