TY  - JOUR
A1  - Lepeta, Katarzyna
A1  - Lourenco, Mychael V.
A1  - Schweitzer, Barbara C.
A1  - Martino Adami, Pamela V.
A1  - Banerjee, Priyanjalee
A1  - Catuara-Solarz, Silvina
A1  - de la Fuente Revenga, Mario
A1  - Marc Guillem, Alain
A1  - Haider, Mouna
A1  - Ijomone, Omamuyovwi M.
A1  - Nadorp, Bettina
A1  - Qi, Lin
A1  - Perera, Nirma D.
A1  - Refsgaard, Louise K.
A1  - Reid, Kimberley M.
A1  - Sabbar, Mariam
A1  - Sahoo, Arghyadip
A1  - Schaefer, Natascha
A1  - Sheean, Rebecca K.
A1  - Suska, Anna
A1  - Verma, Rajkumar
A1  - Vicidomini, Cinzia
A1  - Wright, Dean
A1  - Zhang, Xing-Ding
A1  - Seidenbecher, Constanze
T1  - Synaptopathies: synaptic dysfunction in neurological disorders - a review from students to students
JF  - Journal of Neurochemistry
N2  - Synapses are essential components of neurons and allow information to travel coordinately throughout the nervous system to adjust behavior to environmental stimuli and to control body functions, memories, and emotions. Thus, optimal synaptic communication is required for proper brain physiology, and slight perturbations of synapse function can lead to brain disorders. In fact, increasing evidence has demonstrated the relevance of synapse dysfunction as a major determinant of many neurological diseases. This notion has led to the concept of synaptopathies as brain diseases with synapse defects as shared pathogenic features. In this review, which was initiated at the 13th International Society for Neurochemistry Advanced School, we discuss basic concepts of synapse structure and function, and provide a critical view of how aberrant synapse physiology may contribute to neurodevelopmental disorders (autism, Down syndrome, startle disease, and epilepsy) as well as neurodegenerative disorders (Alzheimer and Parkinson disease). We finally discuss the appropriateness and potential implications of gathering synapse diseases under a single term. Understanding common causes and intrinsic differences in disease-associated synaptic dysfunction could offer novel clues toward synapse-based therapeutic intervention for neurological and neuropsychiatric disorders. In this Review, which was initiated at the 13th International Society for Neurochemistry (ISN) Advanced School, we discuss basic concepts of synapse structure and function, and provide a critical view of how aberrant synapse physiology may contribute to neurodevelopmental (autism, Down syndrome, startle disease, and epilepsy) as well as neurodegenerative disorders (Alzheimer's and Parkinson's diseases), gathered together under the term of synaptopathies. Read the Editorial Highlight for this article on page .
KW  - Amyloid-beta oligomers;
KW  - Central nervous system
KW  - P75 Neurotrophin receptor
KW  - Cellular prion protein
KW  - Temporal-lobe epilepsy
KW  - Familial Alzheimers-disease
KW  - Inhibitory glycine receptor
KW  - Autism spectrum disorders
KW  - Alpha-synuclein oligomers
KW  - Dentate granule cells
KW  - Alzheimer disease
KW  - autism
KW  - Down syndrome
KW  - epilepsy
KW  - hyperekplexia
KW  - synapses
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187509
VL  - 138
IS  - 6
ER  - 
TY  - JOUR
A1  - El Hajj, Nady
A1  - Dittrich, Marcus
A1  - Böck, Julia
A1  - Kraus, Theo F. J.
A1  - Nanda, Indrajit
A1  - Müller, Tobias
A1  - Seidmann, Larissa
A1  - Tralau, Tim
A1  - Galetzka, Danuta
A1  - Schneider, Eberhard
A1  - Haaf, Thomas
T1  - Epigenetic dysregulation in the developing Down syndrome cortex
JF  - Epigenetics
N2  - Using Illumina 450K arrays, 1.85% of all analyzed CpG sites were significantly hypermethylated and 0.31% hypomethylated in fetal Down syndrome (DS) cortex throughout the genome. The methylation changes on chromosome 21 appeared to be balanced between hypo- and hyper-methylation, whereas, consistent with prior reports, all other chromosomes showed 3-11times more hyper- than hypo-methylated sites. Reduced NRSF/REST expression due to upregulation of DYRK1A (on chromosome 21q22.13) and methylation of REST binding sites during early developmental stages may contribute to this genome-wide excess of hypermethylated sites. Upregulation of DNMT3L (on chromosome 21q22.4) could lead to de novo methylation in neuroprogenitors, which then persists in the fetal DS brain where DNMT3A and DNMT3B become downregulated. The vast majority of differentially methylated promoters and genes was hypermethylated in DS and located outside chromosome 21, including the protocadherin gamma (PCDHG) cluster on chromosome 5q31, which is crucial for neural circuit formation in the developing brain. Bisulfite pyrosequencing and targeted RNA sequencing showed that several genes of PCDHG subfamilies A and B are hypermethylated and transcriptionally downregulated in fetal DS cortex. Decreased PCDHG expression is expected to reduce dendrite arborization and growth in cortical neurons. Since constitutive hypermethylation of PCDHG and other genes affects multiple tissues, including blood, it may provide useful biomarkers for DS brain development and pharmacologic targets for therapeutic interventions.
KW  - trisomy 21
KW  - DNA methylation
KW  - Down syndrome
KW  - fetal brain development
KW  - frontal cortex
KW  - protocadherin gamma cluster
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191239
VL  - 11
IS  - 8
ER  - 
TY  - THES
A1  - Lenhard, Wolfgang
T1  - Die psychosoziale Stellung von Eltern behinderter Kinder im Zeitalter der Pränataldiagnostik
T1  - The psychosocial status of families with disabled children in the era of prenatal diagnostics
N2  - Die raschen Fortschritte der medizinischen, insbesondere der genetischen Diagnostik sind für Eltern von Kindern mit Behinderung Fluch und Segen zugleich: Einerseits stellt Unsicherheit hinsichtlich der Ursache der Behinderung für Eltern eine massive Belastung dar, die den Coping-Prozess wesentlich erschwert. Die Ausschöpfung der diagnostischen Möglichkeiten und das dann mögliche Auffinden des Grundes der Behinderung kann den effektiven Einsatz von Bewältigungsstrategien wesentlich erleichtern. Vorgeburtlich dagegen führt ein mit denselben Diagnosemethoden erhobener auffälliger Befund aufgrund des Mangels an therapeutischen Möglichkeiten sehr häufig zum Abbruch der Schwangerschaft. Mittels einer Fragebogenstudie an 925 Eltern von Kindern mit Down-Syndrom, Eltern von Kindern mit einem Kind mit geistiger Behinderung unklarer Ursache und Eltern nicht-behinderter Kinder wurde untersucht, ob diese Entwicklung zur Herausbildung eines neo-eugenischen Automatismus von pränataler Diagnose und Schwangerschaftsabbruch führt, als dessen Folge Menschen mit angeborener Behinderung als „vermeidbare Last“ erscheinen und Eltern von Kindern mit angeborenen Behinderungen gesellschaftlich ausgegrenzt werden.
N2  - The rapid increase of diagnostic possibilities of medicine is at the same time beneficial and threatening for parents of children with disabilities: On the one hand, diagnostic uncertainty is probably one of the greatest single psychological stressors for parents of children with a child with unassigned diagnosis and therefore, the exhaustion of diagnostic possibilities with the option of locating the reason of the handicap can substantially facilitate coping. On the other hand positive findings in prenatal investigations very often results in abortion as no therapeutic options are at hand. This could lead to an automatism of prenatal diagnosis and abortion. In the light of this development congenitally handicapped persons tend to be seen as an "evitable burden", with the consequence of neo-eugenic tendencies in society and the social exclusion of parents. This topic was addressed via a questionnaire study, in which 925 parents of non-disabled children, parents of children with Down syndrome and parents with a mentally retarded child with unknown diagnosis took part.
KW  - Eltern
KW  - Kind
KW  - Behinderung
KW  - Pränatale Diagnostik
KW  - diagnostische Sicherheit
KW  - geistige Behinderung
KW  - unklare Diagnose
KW  - Down-Syndrom
KW  - Pränataldiagnostik
KW  - diagnostic certainty
KW  - mental retardation
KW  - unclear diagnosis
KW  - Down syndrome
KW  - prenatal diagnostic
Y1  - 2004
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-12167
ER  -