White Matter Impairment in Rett Syndrome: Diffusion Tensor Imaging Study with Clinical Correlations

Mahmood, Asif; Bibat, Genila; Zhan, A-Lai; Izbudak, Izlem; Farage, Luciano; Horská, Alena; Mori, Susumu; Naidu, Sakkubai

doi:10.3174/ajnr.a1792

Cited by 58 publications

(40 citation statements)

References 33 publications

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“…Volumetric MRI analyses confirmed a reduction in the whole brain of MeCP2-308 mice (genotype: F(1,15) ¼ 10.81; p ¼ 0.005) (Figure 4c). In agreement with recent imaging studies, which demonstrated a reduction in corpus callosum thickness, associated with white matter pathologic features in RTT patients (Gotoh et al, 2001;Mahmood et al, 2010) (Figures 4a and b) was also found in MeCP2-308 mice. No changes were found in motor cortex of mutant mice and only a trend for increased motor cortex thickness was observed in CNF1-treated mice (F(1,8) ¼ 4.69; p ¼ 0.062) (Figure 4c).…”

Section: Cnf1-induced Brain Morphological and Metabolic Changes In Musupporting

confidence: 92%

Modulation of RhoGTPases Improves the Behavioral Phenotype and Reverses Astrocytic Deficits in a Mouse Model of Rett Syndrome

Filippis

Fabbri

Simone

et al. 2011

Neuropsychopharmacol

109

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RhoGTPases are crucial molecules in neuronal plasticity and cognition, as confirmed by their role in non-syndromic mental retardation. Activation of brain RhoGTPases by the bacterial cytotoxic necrotizing factor 1 (CNF1) reshapes the actin cytoskeleton and enhances neurotransmission and synaptic plasticity in mouse brains. We evaluated the effects of a single CNF1 intracerebroventricular inoculation in a mouse model of Rett syndrome (RTT), a rare neurodevelopmental disorder and a genetic cause of mental retardation, for which no effective therapy is available. Fully symptomatic MeCP2-308 male mice were evaluated in a battery of tests specifically tailored to detect RTT-related impairments. At the end of behavioral testing, brain sections were immunohistochemically characterized. Magnetic resonance imaging and spectroscopy (MRS) were also applied to assess morphological and metabolic brain changes. The CNF1 administration markedly improved the behavioral phenotype of MeCP2-308 mice. CNF1 also dramatically reversed the evident signs of atrophy in astrocytes of mutant mice and restored wt-like levels of this cell population. A partial rescue of the overexpression of IL-6 cytokine was also observed in RTT brains. CNF1-induced brain metabolic changes detected by MRS analysis involved markers of glial integrity and bioenergetics, and point to improved mitochondria functionality in CNF1-treated mice. These results clearly indicate that modulation of brain RhoGTPases by CNF1 may constitute a totally innovative therapeutic approach for RTT and, possibly, for other disorders associated with mental retardation.

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Section: Cnf1-induced Brain Morphological and Metabolic Changes In Musupporting

confidence: 92%

Modulation of RhoGTPases Improves the Behavioral Phenotype and Reverses Astrocytic Deficits in a Mouse Model of Rett Syndrome

Filippis

Fabbri

Simone

et al. 2011

Neuropsychopharmacol

109

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“…To date, there is very little information regarding the brain white matter in RTT, although a recent investigation has evidenced a signifi cant relationship between brain white matter damage (particularly of the superior longitudinal fasciculus, one of the main association bundles connecting the external surface of temporo-parieto-occipital regions with the convexity of the frontal lobe and in part associated with phonologic speech) ( 34,35 ) and ability to speak ( 15 ).…”

Section: Discussionmentioning

confidence: 99%

“…However, in the lack of histological data, it is diffi cult to reach conclusions about the exact mechanism of the fractional anisotropy decrease observed in this patient population. Past studies have suggested axonal involvement to explain fractional anisotropy reduction, but loss of myelin has not been shown to be a contributing factor ( 15 ).…”

Section: Phenotype Severity Scoringmentioning

confidence: 99%

F2-dihomo-isoprostanes as potential early biomarkers of lipid oxidative damage in Rett syndrome

Felice

Signorini

Durand

et al. 2011

Journal of Lipid Research

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“…Trata-se da Síndrome de Rett, uma encefalopatia infantil crônica e progressiva que afeta, quase exclusivamente, crianças do sexo feminino. Nos casos clássi-cos, as manifestações clínicas são observadas nos primeiros meses de vida com comprometimento motor progressivo (Mahmood et al 2010).…”

Section: Introductionunclassified

“…Tanto a DE, quanto a forma clássica da Síndrome de Rett (Mahmood et al 2010), só ocorrem em fêmeas. Clinicamente, as duas enfermidades cursam com desordem neurológica crônica, acompanhada de anormalidades posturais com desvio da coluna vertebral.…”

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Encefalopatia hereditária em bovinos no estado do Espírito Santo

et al. 2011

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723Pesq. Vet. Bras. 31(9):723-730, setembro 2011 RESUMO.-Descrevem-se os aspectos epidemiológicos e clí-nico-necroscópicos de uma doença neurológica hereditária observada em bovinos no município de Ecoporanga, norte do Estado do Espírito Santo. Trata-se de enfermidade do sistema nervoso central verificada exclusivamente em fêmeas, filhas de touro reprodutor de 5 anos de idade da raça Nelore, oriundo do município de Curvelo, Minas Gerais, com vacas mestiças Nelore x Quianini; bezerros machos oriundos deste cruzamento não demonstraram quaisquer sinais relacionados à enfermidade. Os sinais clínicos, presentes ao nascimento ou detectáveis nas primeiras semanas de vida, caracterizamse por ataxia, perda do equilíbrio, instabilidade, andar em cír-culos, posicionamento incorreto dos membros no animal em estação ou em marcha (afastamento e/ou desvio de membros da posição normal) e desvio lateral da coluna (eixo principal do corpo em diagonal). De animal para animal, há marcada variação na intensidade das manifestações clínicas. Os bovinos mais afetados morrem devido à incapacidade de se alimentar. O exame macroscópico evidenciou, em grau variável de intensidade, áreas de depressão assimétrica setorial, sobretudo nos lobos frontal e temporal do córtex telencefálico e no córtex cerebelar. Em adição observou-se atrofia de grupos musculares de membros correspondentes às porções defeituosas no sistema nervoso central. O estudo histológico inicial revelou que as áreas deprimidas devem-se à re-

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White Matter Impairment in Rett Syndrome: Diffusion Tensor Imaging Study with Clinical Correlations

Abstract: BACKGROUND AND PURPOSE:RTT, caused by mutations in the methyl CPG binding protein 2 (MeCP2) gene, is a disorder of neuronal maturation and connections. Our aim was to prospectively examine FA by DTI and correlate this with certain clinical features in patients with RTT.

Cited by 58 publications

References 33 publications

Modulation of RhoGTPases Improves the Behavioral Phenotype and Reverses Astrocytic Deficits in a Mouse Model of Rett Syndrome

Modulation of RhoGTPases Improves the Behavioral Phenotype and Reverses Astrocytic Deficits in a Mouse Model of Rett Syndrome

F2-dihomo-isoprostanes as potential early biomarkers of lipid oxidative damage in Rett syndrome

Encefalopatia hereditária em bovinos no estado do Espírito Santo

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