Deficient Purposeful Use of Forepaws in Female Mice Modelling Rett Syndrome
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...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2015/326184 |
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| author | Bianca De Filippis Mattia Musto Luisa Altabella Emilia Romano Rossella Canese Giovanni Laviola |
| author_facet | Bianca De Filippis Mattia Musto Luisa Altabella Emilia Romano Rossella Canese Giovanni Laviola |
| author_sort | Bianca De Filippis |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2e61de9b2ea3415aaaa33f410f66bd95 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-2e61de9b2ea3415aaaa33f410f66bd952025-02-03T01:04:45ZengWileyNeural Plasticity2090-59041687-54432015-01-01201510.1155/2015/326184326184Deficient Purposeful Use of Forepaws in Female Mice Modelling Rett SyndromeBianca De Filippis0Mattia Musto1Luisa Altabella2Emilia Romano3Rossella Canese4Giovanni Laviola5Behavioural Neuroscience Section, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyBehavioural Neuroscience Section, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyMolecular and Cellular Imaging Section, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyBehavioural Neuroscience Section, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyMolecular and Cellular Imaging Section, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyBehavioural Neuroscience Section, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyRett 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.http://dx.doi.org/10.1155/2015/326184 |
| spellingShingle | Bianca De Filippis Mattia Musto Luisa Altabella Emilia Romano Rossella Canese Giovanni Laviola Deficient Purposeful Use of Forepaws in Female Mice Modelling Rett Syndrome Neural Plasticity |
| title | Deficient Purposeful Use of Forepaws in Female Mice Modelling Rett Syndrome |
| title_full | Deficient Purposeful Use of Forepaws in Female Mice Modelling Rett Syndrome |
| title_fullStr | Deficient Purposeful Use of Forepaws in Female Mice Modelling Rett Syndrome |
| title_full_unstemmed | Deficient Purposeful Use of Forepaws in Female Mice Modelling Rett Syndrome |
| title_short | Deficient Purposeful Use of Forepaws in Female Mice Modelling Rett Syndrome |
| title_sort | deficient purposeful use of forepaws in female mice modelling rett syndrome |
| url | http://dx.doi.org/10.1155/2015/326184 |
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