Boosting Serotonin Synthesis Is Not Sufficient to Improve Motor Coordination of Heterozygous Mouse Model of Rett Syndrome.

Motor deficit is a core symptom of Rett syndrome, a rare neurological disease caused in most cases by mutations of the () gene. Serotonin reuptake inhibitors improve motor coordination in heterozygous (Het) mice and serotonin depletion prevented this effect. Here, we assess alterations in indole levels in various brain regions and whether boosting brain serotonin synthesis with the serotonin precursors tryptophan, 5-hydroxytryptophan and α-lactalbumin rescued motor coordination deficit of Het mice. Motor coordination was assessed in the accelerated rotarod during and after systemic administration of serotonin precursors for 2-3 weeks. Since no data are available, the effect of α-lactalbumin on tryptophan, serotonin and 5-hydroxyindoleacetic acid levels was evaluated in various brain regions in order to identify the dose of ALAC to evaluate on motor coordination. As compared to WT, Het mice show reduced levels of serotonin in the whole brain, hippocampus, brainstem and cerebral cortex, but not the striatum. Reduced levels of 5-hydroxyindoleacetic acid were observed in the hippocampus and brainstem. Doses of serotonin precursors increasing brain tryptophan and/or serotonin production and metabolism had no effect on motor coordination. The results indicate that boosting serotonin synthesis is not sufficient to improve motor coordination of Het mice.