Molecular changes in fetal Down syndrome brain

Engidawork, Ephrem; Lubec, Gert

doi:10.1046/j.1471-4159.2003.01614.x

Cited by 88 publications

(42 citation statements)

References 68 publications

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“…Many of the brain/neurological abnormalities associated with Down syndrome are not detected until postnatal or adult life and have not been described for Ts16 mice due to embryonic lethality (Lane et al, 1996;Engidawork and Lubec, 2003). However, the increased expression of DSCR1 and decreased NFAT activation observed in the brain of Ts16 embryos may be related to compromised cognitive function later in life.…”

Section: Discussionmentioning

confidence: 99%

Restoration of DSCR1 to disomy in the trisomy 16 mouse model of Down syndrome does not correct cardiac or craniofacial development anomalies

Lange

Rothermel

Yutzey

2005

Developmental Dynamics

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The Down syndrome critical region 1 (DSCR1) gene is located in syntenic regions of human chromosome 21 and mouse chromosome 16 and encodes a regulatory protein in the calcineurin/NFAT pathway. DSCR1 expression in the embryonic brain, craniofacial structures, and heart is consistent with a role in contributing to Down syndrome developmental anomalies. In the trisomy 16 (Ts16) murine model of Down syndrome, expression of DSCR1 isoforms is elevated and NFAT transcriptional activity is decreased in the developing heart and brain. The individual contribution of DSCR1 to Down syndrome-related anomalies was examined by specific restoration of DSCR1 to disomic levels in Ts16 embryos. However, genetic restoration of DSCR1 did not rescue major morphological abnormalities in cardiac or craniofacial development. These data demonstrate that trisomy of DSCR1 alone does not significantly contribute to developmental defects in Ts16 mice and underscore the complexity of developmental anomalies associated with Down syndrome. Developmental Dynamics 233:954 -963, 2005.

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Section: Discussionmentioning

confidence: 99%

Restoration of DSCR1 to disomy in the trisomy 16 mouse model of Down syndrome does not correct cardiac or craniofacial development anomalies

Lange

Rothermel

Yutzey

2005

Developmental Dynamics

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“…As the first manifestation of neuroanatomical abnormality, a characteristic reduced brain size of children with DS appears in the 4-to 5-month fetus and progresses during the last 3 months of gestation [9,10]. Structural MRI reports, based on fewer than 15 original studies in children and youths, have suggested that the total brain volume is smaller [11][12][13][14], with specific reductions in cerebellar [11][12][13]15] and hippocampal volumes [12,14,15].…”

Section: Introductionmentioning

confidence: 99%

Structural brain alterations of Down’s syndrome in early childhood evaluation by DTI and volumetric analyses

et al. 2016

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Objectives To provide an initial assessment of white matter (WM) integrity with diffusion tensor imaging (DTI) and the accompanying volumetric changes in WM and grey matter (GM) through volumetric analyses of young children with Down's syndrome (DS). Methods Ten children with DS and eight healthy control subjects were included in the study. Tract-based spatial statistics (TBSS) were used in the DTI study for whole-brain voxelwise analysis of fractional anisotropy (FA) and mean diffusivity (MD) of WM. Volumetric analyses were performed with an automated segmentation method to obtain regional measurements of cortical volumes. Results Children with DS showed significantly reduced FA in association tracts of the fronto-temporo-occipital regions as well as the corpus callosum (CC) and anterior limb of the internal capsule (p < 0.05). Volumetric reductions included total cortical GM, cerebellar GM and WM volume, basal ganglia, thalamus, brainstem and CC in DS compared with controls (p < 0.05). Conclusion These preliminary results suggest that DTI and volumetric analyses may reflect the earliest complementary changes of the neurodevelopmental delay in children with DS and can serve as surrogate biomarkers of the specific elements of WM and GM integrity for cognitive development. Key Points• DS is the most common genetic cause of intellectual disability.• WM and GM structural alterations represent the neurological features of DS.• DTI may identify the earliest aging process changes.• DTI-volumetric analyses can serve as surrogate biomarkers of neurodevelopment in DS.

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“…The gene dosage hypothesis claims that genes encoded on chromosome 21 are expressed 1.5 times higher in DS and thus lead to the development of the DS phenotype [3,4]. However, several groups, including ours, Ferrando-Miguel/Shim/Cheon/Gimona/ Furuse/Lubec have challenged this hypothesis at the protein level [5][6][7][8][9]. It may well be that genes encoded on chromosome 21 are upregulated by a factor of 1.5 at the nucleic acid level, but no prediction about gene products, i.e.…”

Section: Introductionmentioning

confidence: 94%

Overexpression of Interferon α/β Receptor β Chain in Fetal Down Syndrome Brain

Ferrando-Miguel¹,

Shim²,

Cheon³

et al. 2003

Neuroembryol Aging

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Background: Down syndrome (DS; trisomy 21) is the most common chromosomal aberration, with an incidence of 1/700 live births, and presents with mental retardation, typical phenotype and a series of associated pathological conditions. Although overexpression of genes encoded on chromosome 21 was proposed to lead to the phenotype, this has not been fully addressed at the protein level. Aim: It was therefore the aim of our study to determine protein levels of several chromosome 21 gene products in fetal DS brain. We selected interferon (IFN) α/β receptor β chain (IFNAR2), glutamate receptor 5 (ionotropic kainate 1), h2 calponin, claudin-8 and oligodendrocyte transcription factor 1 for quantification in fetal brain of the early second trimester using immunoblotting. Results: We observed significant and about twofold overexpression of the 20-kD immunoreactive IFN receptor α/β band in the fetal cortex of DS brain (p = 0.0293), while the 70-kD immunoreactive band was overexpressed but did not reach statistical significance (p = 0.065). When data were normalized to the housekeeping protein β-actin, a significant increase in IFN receptor levels was observed. Levels of the aforementioned proteins were comparable between DS and controls. Conclusion: Overexpression of IFNAR2 in fetal DS brain may increase the responsiveness of DS cells, leading to altered neuronal excitability, neuronal growth and survival as well as cytoskeleton derangement.

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Molecular changes in fetal Down syndrome brain

Cited by 88 publications

References 68 publications

Restoration of DSCR1 to disomy in the trisomy 16 mouse model of Down syndrome does not correct cardiac or craniofacial development anomalies

Restoration of DSCR1 to disomy in the trisomy 16 mouse model of Down syndrome does not correct cardiac or craniofacial development anomalies

Structural brain alterations of Down’s syndrome in early childhood evaluation by DTI and volumetric analyses

Overexpression of Interferon α/β Receptor β Chain in Fetal Down Syndrome Brain

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