title: Deletion of the STOP gene, a microtubule stabilizing factor, leads only to discrete cerebral metabolic changes in mice.
abstract: In mice, deletion of the STOP protein leads to subtle anatomic changes and induces depleted synaptic vesicle pools, impaired synaptic plasticity, hyperdopaminergy, and major behavioral disorders alleviated by neuroleptics, hence leading to a schizophrenic-like phenotype. In this study, we applied the quantitative autoradiographic [(14)C]2-deoxyglucose technique to study to what extent the basal rate of cerebral glucose utilization in STOP-knockout (STOP-KO) mice occurs in regions where metabolic changes have been reported in schizophrenic patients. Studies were performed on wild-type, heterozygous, and homozygous STOP-KO mice (7-8 per group). Mice were implanted with femoral artery and vein catheters, and cerebral glucose utilization was quantified over 45 min. Compared with that in wild-type mice, glucose utilization in STOP-KO mice was significantly increased in the olfactory cortex, ventromedial and anterolateral hypothalamus, ventral tegmental area, and substantia nigra pars compacta. Nonsignificant increases, ranging between 9% and 19%, were recorded in the whole auditory system, CA1 pyramidal cell layer, and dorsal raphe. Glucose utilization was also significantly increased in heterozygous mice compared with that in wild-type mice in olfactory cortex. These data might reflect hyperdopaminergic activity, olfactory deficits, and sleep disturbances in STOP-KO mice that have also been reported in schizophrenic patients.
authors.affiliation: INSERM U 666, Strasbourg, France.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Hanaya
authors.forename: Estelle
authors.initials: E
authors.lastname: Koning
authors.forename: Arielle
authors.initials: A
authors.lastname: Ferrandon
authors.forename: Annie
authors.initials: A
authors.lastname: Schweitzer
authors.forename: Annie
authors.initials: A
authors.lastname: Andrieux
authors.forename: Astrid
authors.initials: A
authors.lastname: Nehlig
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D008869:Microtubule-Associated Proteins; C491893:Mtap6 protein, mouse; D005947:Glucose