Deletion of the STOP gene, a microtubule stabilizing factor, leads only to discrete cerebral metabolic changes in mice.

Ryosuke Hanaya (1) , Estelle Koning (1) , Arielle Ferrandon (1) , Annie Schweitzer (2) , Annie Andrieux (2) , Astrid Nehlig (1)

1 Physiopathologie clinique et expérimentale de la schizophrénie
2 Organisation Fonctionnelle du Cytosquelette

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.

Mots clés: cerebral glucose metabolism; cytoskeleton; microtubules; STOP protein; schizophrenia; transgenic mice

Domaines: Neurosciences [q-bio.NC]; Biochimie, Biologie Moléculaire

Ryosuke Hanaya, Estelle Koning, Arielle Ferrandon, Annie Schweitzer, Annie Andrieux, et al.. Deletion of the STOP gene, a microtubule stabilizing factor, leads only to discrete cerebral metabolic changes in mice.. Journal of Neuroscience Research, 2008, 86 (4), pp.813-20. ⟨10.1002/jnr.21550⟩. ⟨inserm-00375633⟩