TY  - JOUR
A1  - Neuhaus, Winfried
A1  - Schlundt, Marian
A1  - Fehrholz, Markus
A1  - Ehrke, Alexander
A1  - Kunzmann, Steffen
A1  - Liebner, Stefan
A1  - Speer, Christian P.
A1  - Förster, Carola Y.
T1  - Multiple antenatal dexamethasone treatment alters brain vessel differentiation in newborn mouse pups
JF  - PLoS ONE
N2  - Antenatal steroid treatment decreases morbidity and mortality in premature infants through the maturation of lung tissue, which enables sufficient breathing performance. However, clinical and animal studies have shown that repeated doses of glucocorticoids such as dexamethasone and betamethasone lead to long-term adverse effects on brain development. Therefore, we established a mouse model for antenatal dexamethasone treatment to investigate the effects of dexamethasone on brain vessel differentiation towards the blood-brain barrier (BBB) phenotype, focusing on molecular marker analysis. The major findings were that in total brains on postnatal day (PN) 4 triple antenatal dexamethasone treatment significantly downregulated the tight junction protein claudin-5, the endothelial marker Pecam-1/CD31, the glucocorticoid receptor, the NR1 subunit of the N-methyl-D-aspartate receptor, and Abc transporters (Abcb1a, Abcg2 Abcc4). Less pronounced effects were found after single antenatal dexamethasone treatment and in PN10 samples. Comparisons of total brain samples with isolated brain endothelial cells together with the stainings for Pecam-1/CD31 and claudin-5 led to the assumption that the morphology of brain vessels is affected by antenatal dexamethasone treatment at PN4. On the mRNA level markers for angiogenesis, the sonic hedgehog and the Wnt pathway were downregulated in PN4 samples, suggesting fundamental changes in brain vascularization and/or differentiation. In conclusion, we provided a first comprehensive molecular basis for the adverse effects of multiple antenatal dexamethasone treatment on brain vessel differentiation.
KW  - preterm birth
KW  - fetal lung
KW  - corticosteroids
KW  - glucocorticoids
KW  - exposure
KW  - endothelial cells
KW  - in vitro
KW  - barrier
KW  - expression
KW  - rat
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148268
VL  - 10
IS  - 8
ER  - 
TY  - JOUR
A1  - Girschick, Hermann
A1  - Wolf, Christine
A1  - Morbach, Henner
A1  - Hertzberg, Christoph
A1  - Lee-Kirsch, Min Ae
T1  - Severe immune dysregulation with neurological impairment and minor bone changes in a child with spondyloenchondrodysplasia due to two novel mutations in the ACP5 gene
JF  - Pediatric Rheumatology
N2  - Spondyloenchondrodysplasia (SPENCD) is a rare skeletal dysplasia, characterized by metaphyseal lesions, neurological impairment and immune dysregulation associated with lupus-like features. SPENCD is caused by biallelic mutations in the ACP5 gene encoding tartrate-resistant phosphatase. We report on a child, who presented with spasticity, multisystem inflammation, autoimmunity and immunodeficiency with minimal metaphyseal changes due to compound heterozygosity for two novel ACP5 mutations. These findings extend the phenotypic spectrum of SPENCD and indicate that ACP5 mutations can cause severe immune dysregulation and neurological impairment even in the absence of metaphyseal dysplasia.
KW  - resistant acid phosphatase
KW  - expression
KW  - systemic lupus erythematosus
KW  - cerebral calcification
KW  - deficiency
KW  - autoimmunity
KW  - dysplasia
KW  - trap
KW  - spondyloenchondrodysplasia
KW  - ACP5
KW  - immunodeficiency
KW  - type I interferonopathy
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-149990
VL  - 13
IS  - 37
ER  -