title: Repeated corticosterone injections in adult mice alter stress hormonal receptor expression in the cerebellum and motor coordination without affecting spatial learning.
abstract: Receptors for glucocorticoid (GR) and corticotropin-releasing hormone (CRH) are largely found in brain sensorimotor structures, particularly in cerebellum, underlining a potential role of stress hormones in the regulation of motor function. Since CRH is involved in neuroplasticity, known for its trophic effect on synapses, we investigated how manipulations in corticosterone serum levels can modulate the CRH system in the cerebellum and affect motor coordination. Corticosterone at doses of either 15 or 30mg/kg was injected in mice and the status of hormonal expression evaluated in cerebellum, hippocampus, and hypothalamus in undisturbed housing conditions or after different behavioral tests. Under both conditions, metabolic activity in numerous brain regions involved in motor functions and emotion was measured by means of cytochrome oxidase (COX) activity labeling. After six consecutive days of corticosterone administration, CRH-R1 transcription was downregulated in hypothalamic and cerebellar regions and hypometabolic changes were observed in mice treated with the higher dose for several limbic and sensorimotor circuitries, notably basal ganglia, deep cerebellar nuclei, and red nucleus. Corticosterone did not modify motor activity, anxiety, and spatial orientation, but decreased latencies before falling from the rotorod and prevented mice from reaching targets in the coat-hanger test. In addition, COX activities were similar to control mice except in ventromedial thalamus and dorsal neostriatum, possibly indicating that physical activity protected brain energy metabolism against the stress hormone. The present findings showed that the CRH/CRH-R1 system might play a role in mediating the effects of stress on cerebellar function, affecting especially motor learning tasks.
authors.affiliation: EA7300, Lab. «Stress, Immunity, Pathogens», Lorraine University, 54500 Vandoeuvre-les-Nancy, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Harlé
authors.affiliation: EA4699, Lab. ICONES, University of Rouen, 76821 Mont-Saint-Aignan, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Lalonde
authors.affiliation: EA7300, Lab. «Stress, Immunity, Pathogens», Lorraine University, 54500 Vandoeuvre-les-Nancy, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Fonte
authors.affiliation: EA7300, Lab. «Stress, Immunity, Pathogens», Lorraine University, 54500 Vandoeuvre-les-Nancy, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Ropars
authors.affiliation: EA7300, Lab. «Stress, Immunity, Pathogens», Lorraine University, 54500 Vandoeuvre-les-Nancy, France.
authors.forename: Jean-Pol
authors.initials: JP
authors.lastname: Frippiat
authors.affiliation: EA7300, Lab. «Stress, Immunity, Pathogens», Lorraine University, 54500 Vandoeuvre-les-Nancy, France; Service of Microscopy, Lorraine University, 54500 Vandoeuvre-les-Nancy, France; CHRU de Nancy, 54500 Vandoeuvre-les-Nancy, France. Electronic address: catherine.strazielle@univ-lorraine.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Strazielle
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism*; D003345:Corticosterone / Q000008:administration & dosage / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011597:Psychomotor Performance / Q000187:drug effects*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000187:drug effects*; D065853:Spatial Learning / Q000187:drug effects*
chemical_list: D005938:Glucocorticoids; D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone
keywords: Brain metabolism; Cognitive function; Corticotropin releasing hormone; Glucocorticoid; Motor coordination