title: Deficient Purposeful Use of Forepaws in Female Mice Modelling Rett Syndrome.
abstract: Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioural and physiological symptoms. Mutations in the methyl CpG binding protein 2 gene (MECP2) cause more than 95% of classic cases. Motor abnormalities represent a significant part of the spectrum of RTT symptoms. In the present study we investigated motor coordination and fine motor skill domains in MeCP2-308 female mice, a validated RTT model. This was complemented by the in vivo magnetic resonance spectroscopy (MRS) analysis of metabolic profile in behaviourally relevant brain areas. MeCP2-308 heterozygous female mice (Het, 10-12 months of age) were impaired in tasks validated for the assessment of purposeful and coordinated forepaw use (Morag test and Capellini handling task). A fine-grain analysis of spontaneous behaviour in the home-cage also revealed an abnormal handling pattern when interacting with the nesting material, reduced motivation to explore the environment, and increased time devoted to feeding in Het mice. The brain MRS evaluation highlighted decreased levels of bioenergetic metabolites in the striatal area in Het mice compared to controls. Present results confirm behavioural and brain alterations previously reported in MeCP2-308 males and identify novel endpoints on which the efficacy of innovative therapeutic strategies for RTT may be tested.
authors.affiliation: Behavioural Neuroscience Section, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Bianca
authors.initials: B
authors.lastname: De Filippis
authors.affiliation: Behavioural Neuroscience Section, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Musto
authors.affiliation: Molecular and Cellular Imaging Section, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Altabella
authors.affiliation: Behavioural Neuroscience Section, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Emilia
authors.initials: E
authors.lastname: Romano
authors.affiliation: Molecular and Cellular Imaging Section, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Canese
authors.affiliation: Behavioural Neuroscience Section, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Laviola
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight / Q000235:genetics; D001923:Brain Chemistry / Q000502:physiology; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005260:Female; D005552:Forelimb; D005838:Genotype; D009682:Magnetic Resonance Spectroscopy; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D051379:Mice; D009042:Motivation; D009048:Motor Skills; D017072:Neostriatum / Q000378:metabolism; D009425:Nesting Behavior; D011597:Psychomotor Performance; D015518:Rett Syndrome / Q000235:genetics / Q000523:psychology*
chemical_list: C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2