1. Dansie LE, Phommahaxay K, Okusanya AG, Uwadia J, Huang M, Rotschafer SE, Razak KA, Ethell DW, Ethell IM. {{Long-lasting Effects of Minocycline on Behavior in Young but not Adult Fragile X Mice}}. {Neuroscience};2013 (May 6)
Fragile X Syndrome (FXS) is the most common single-gene inherited form of intellectual disability with behaviors characteristic of autism. People with FXS display childhood seizures, hyperactivity, anxiety, developmental delay, attention deficits, and visual-spatial memory impairment, as well as a propensity for obsessive-compulsive disorder (OCD). Several of these aberrant behaviors and FXS-associated synaptic irregularities also occur in « fragile X mental retardation gene » knock-out (Fmr1 KO) mice. We previously reported that minocycline promotes the maturation of dendritic spines – postsynaptic sites for excitatory synapses – in the developing hippocampus of Fmr1 KO mice, which may underlie the beneficial effects of minocycline on anxiolytic behavior in young Fmr1 KO mice. In this study, we compared the effectiveness of minocycline treatment in young and adult Fmr1 KO mice, and determined the dependence of behavioral improvements on short-term versus long-term minocycline administration. We found that 4 and 8 week long treatments significantly reduced locomotor activity in both young and adult Fmr1 KO mice. Some behavioral improvements persisted in young mice post-treatment, but in adults the beneficial effects were lost soon after minocycline treatment was stopped. We also show, for the first time, that minocycline treatment partially attenuates the number and severity of audiogenic seizures in Fmr1 KO mice. This report provides further evidence that minocycline treatment has immediate and long-lasting benefits on FXS-associated behaviors in the Fmr1 KO mouse model.
Lien vers le texte intégral (Open Access ou abonnement)
2. Jolley A, Corbett M, McGregor L, Waters W, Brown S, Nicholl J, Yu S. {{De Novo Intragenic Deletion of the Autism Susceptibility Candidate 2 (AUTS2) Gene in a Patient With Developmental Delay: A Case Report and Literature Review}}. {Am J Med Genet A};2013 (May 6)
Lien vers le texte intégral (Open Access ou abonnement)
3. Lafauci G, Adayev T, Kascsak R, Nolin S, Mehta P, Brown WT, Dobkin C. {{Fragile X Screening: Quantification of FMRP in Dried Blood Spots by a Luminex Immunoassay}}. {J Mol Diagn};2013 (May 6)
Fragile X is the most common inherited cause of intellectual disability and is frequently associated with autism. The syndrome is due to mutations of the FMR1 gene that result in the absence of fragile X mental retardation protein (FMRP). We have developed a rapid, highly sensitive method for quantifying FMRP from dried blood spots and lymphocytes. This assay uses two new antibodies, a bacterially expressed abbreviated FMRP standard, and a Luminex platform to quantify FMRP. The assay readily distinguished between samples from males with fragile X full mutations and samples from normal males. It also differentiated mosaic from nonmosaic full-mutation male samples. This assay, because of its methodology and minimal cost, could be the basis for newborn or population screening.
Lien vers le texte intégral (Open Access ou abonnement)
4. Wang JY, Hagerman RJ, Rivera SM. {{A multimodal imaging analysis of subcortical gray matter in fragile X premutation carriers}}. {Mov Disord};2013 (May 6)
Approximately 40% of males with the fragile X premutation develop fragile X-associated tremor/ataxia syndrome after age 50. Although the thalamus and basal ganglia play a crucial role in movement disorders, their involvement in fragile X premutation carriers has not been systematically investigated. The current study characterized structural abnormalities associated with fragile X premutation carriers (with and without fragile X-associated tremor/ataxia syndrome) in the thalamus, caudate nucleus, putamen, and globus pallidus using T1-weighted and diffusion tensor imaging. Male premutation carriers with fragile X-associated tremor/ataxia syndrome showed significant volume atrophy and diffusion-weighted signal loss in all 4 structures compared with the control group. They also exhibited volume atrophy and diffusion-weighted signal loss in the thalamus and striatum compared with the premutation carriers without fragile X-associated tremor/ataxia syndrome. Importantly, many of the measurements exhibited robust correlations with symptom severity, with volume and diffusion-weighted imaging measurements displaying negative correlations and fractional anisotropy measurements displaying positive correlations. The current study demonstrated involvement of all 4 subcortical gray matter structures in fragile X-associated tremor/ataxia syndrome, with significant volume atrophy, and possible iron deposition indicated by the diffusion-weighted signal loss. The significant correlation between the subcortical measurements and symptom severity suggests the benefits of tracking structural changes in subcortical gray matter in future longitudinal studies for early detection and disease monitoring. (c) 2013 Movement Disorder Society.
