| First Author | Valenti D | Year | 2017 |
| Journal | Neuropharmacology | Volume | 121 |
| Pages | 79-88 | PubMed ID | 28419872 |
| Mgi Jnum | J:337257 | Mgi Id | MGI:5927297 |
| Doi | 10.1016/j.neuropharm.2017.04.024 | Citation | Valenti D, et al. (2017) Stimulation of the brain serotonin receptor 7 rescues mitochondrial dysfunction in female mice from two models of Rett syndrome. Neuropharmacology 121:79-88 |
| abstractText | Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioral and physiological symptoms. Mutations in the methyl CpG binding protein 2 gene (MECP2) cause more than 95% of classic cases, and currently there is no cure for this devastating disorder. Recently we have demonstrated that neurobehavioral and brain molecular alterations can be rescued in a RTT mouse model, by pharmacological stimulation of the brain serotonin receptor 7 (5-HT7R). This member of the serotonin receptor family, crucially involved in the regulation of brain structural plasticity and cognitive processes, can be stimulated by systemic repeated treatment with LP-211, a brain-penetrant selective agonist. The present study extends previous findings by demonstrating that LP-211 treatment (0.25 mg/kg, once per day for 7 days) rescues mitochondrial respiratory chain impairment, oxidative phosphorylation deficiency and the reduced energy status in the brain of heterozygous female mice from two highly validated mouse models of RTT (MeCP2-308 and MeCP2-Bird mice). Moreover, LP-211 treatment completely restored the radical species overproduction by brain mitochondria in the MeCP2-308 model and partially recovered the oxidative imbalance in the more severely affected MeCP2-Bird model. These results provide the first evidence that RTT brain mitochondrial dysfunction can be rescued targeting the brain 5-HT7R and add compelling preclinical evidence of the potential therapeutic value of LP-211 as a pharmacological approach for this devastating neurodevelopmental disorder. |
