TY  - JOUR
A1  - McFleder, Rhonda L.
A1  - Makhotkina, Anastasiia
A1  - Groh, Janos
A1  - Keber, Ursula
A1  - Imdahl, Fabian
A1  - Peña Mosca, Josefina
A1  - Peteranderl, Alina
A1  - Wu, Jingjing
A1  - Tabuchi, Sawako
A1  - Hoffmann, Jan
A1  - Karl, Ann-Kathrin
A1  - Pagenstecher, Axel
A1  - Vogel, Jörg
A1  - Beilhack, Andreas
A1  - Koprich, James B.
A1  - Brotchie, Jonathan M.
A1  - Saliba, Antoine-Emmanuel
A1  - Volkmann, Jens
A1  - Ip, Chi Wang
T1  - Brain-to-gut trafficking of alpha-synuclein by CD11c\(^+\) cells in a mouse model of Parkinson’s disease
JF  - Nature Communications
N2  - Inflammation in the brain and gut is a critical component of several neurological diseases, such as Parkinson’s disease (PD). One trigger of the immune system in PD is aggregation of the pre-synaptic protein, α-synuclein (αSyn). Understanding the mechanism of propagation of αSyn aggregates is essential to developing disease-modifying therapeutics. Using a brain-first mouse model of PD, we demonstrate αSyn trafficking from the brain to the ileum of male mice. Immunohistochemistry revealed that the ileal αSyn aggregations are contained within CD11c+ cells. Using single-cell RNA sequencing, we demonstrate that ileal CD11c\(^+\) cells are microglia-like and the same subtype of cells is activated in the brain and ileum of PD mice. Moreover, by utilizing mice expressing the photo-convertible protein, Dendra2, we show that CD11c\(^+\) cells traffic from the brain to the ileum. Together these data provide a mechanism of αSyn trafficking between the brain and gut.
KW  - antigen-presenting cells
KW  - neuroimmunology
KW  - Parkinson's disease
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357696
VL  - 14
ER  - 
TY  - JOUR
A1  - Schulz, Herbert
A1  - Ruppert, Ann-Kathrin
A1  - Herms, Stefan
A1  - Wolf, Christiane
A1  - Mirza-Schreiber, Nazanin
A1  - Stegle, Oliver
A1  - Czamara, Darina
A1  - Forstner, Andreas J.
A1  - Sivalingam, Sugirthan
A1  - Schoch, Susanne
A1  - Moebus, Susanne
A1  - Pütz, Benno
A1  - Hillmer, Axel
A1  - Fricker, Nadine
A1  - Vatter, Hartmut
A1  - Müller-Myhsok, Bertram
A1  - Nöthen, Markus M.
A1  - Becker, Albert J.
A1  - Hoffmann, Per
A1  - Sander, Thomas
A1  - Cichon, Sven
T1  - Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus
JF  - Nature Communications
N2  - Emerging evidence emphasizes the strong impact of regulatory genomic elements in neurodevelopmental processes and the complex pathways of brain disorders. The present genome-wide quantitative trait loci analyses explore the \(cis\)-regulatory effects of single-nucleotide polymorphisms (SNPs) on DNA methylation (meQTL) and gene expression (eQTL) in 110 human hippocampal biopsies. We identify \(cis\)-meQTLs at 14,118 CpG methylation sites and \(cis\)-eQTLs for 302 3′-mRNA transcripts of 288 genes. Hippocampal \(cis\)-meQTL-CpGs are enriched in flanking regions of active promoters, CpG island shores, binding sites of the transcription factor CTCF and brain eQTLs. \(Cis\)-acting SNPs of hippocampal meQTLs and eQTLs significantly overlap schizophrenia-associated SNPs. Correlations of CpG methylation and RNA expression are found for 34 genes. Our comprehensive maps of \(cis\)-acting hippocampal meQTLs and eQTLs provide a link between disease-associated SNPs and the regulatory genome that will improve the functional interpretation of non-coding genetic variants in the molecular genetic dissection of brain disorders.
KW  - psychiatry
KW  - epigenetics in the nervous system
KW  - epigenomics
KW  - gene expression
KW  - neurological disorders
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173168
VL  - 8
ER  - 
TY  - JOUR
A1  - Jeanclos, Elisabeth
A1  - Knobloch, Gunnar
A1  - Hoffmann, Axel
A1  - Fedorchenko, Oleg
A1  - Odersky, Andrea
A1  - Lamprecht, Anna‐Karina
A1  - Schindelin, Hermann
A1  - Gohla, Antje
T1  - Ca\(^{2+}\) functions as a molecular switch that controls the mutually exclusive complex formation of pyridoxal phosphatase with CIB1 or calmodulin
JF  - FEBS Letters
N2  - Pyridoxal 5′‐phosphate (PLP) is an essential cofactor for neurotransmitter metabolism. Pyridoxal phosphatase (PDXP) deficiency in mice increases PLP and γ‐aminobutyric acid levels in the brain, yet how PDXP is regulated is unclear. Here, we identify the Ca\(^{2+}\)‐ and integrin‐binding protein 1 (CIB1) as a PDXP interactor by yeast two‐hybrid screening and find a calmodulin (CaM)‐binding motif that overlaps with the PDXP‐CIB1 interaction site. Pulldown and crosslinking assays with purified proteins demonstrate that PDXP directly binds to CIB1 or CaM. CIB1 or CaM does not alter PDXP phosphatase activity. However, elevated Ca\(^{2+}\) concentrations promote CaM binding and, thereby, diminish CIB1 binding to PDXP, as both interactors bind in a mutually exclusive way. Hence, the PDXP‐CIB1 complex may functionally differ from the PDXP‐Ca\(^{2+}\)‐CaM complex.
KW  - calmodulin
KW  - chronophin
KW  - CIB1
KW  - haloacid dehalogenase
KW  - pyridoxal phosphatase
KW  - vitamin B6
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-217963
VL  - 594
IS  - 13
SP  - 2099
EP  - 2115
ER  - 
TY  - JOUR
A1  - Künstner, Axel
A1  - Hoffmann, Margarete
A1  - Fraser, Bonnie A.
A1  - Kottler, Verena A.
A1  - Sharma, Eshita
A1  - Weigel, Detlef
A1  - Dreyer, Christine
T1  - The Genome of the Trinidadian Guppy, Poecilia reticulata, and Variation in the Guanapo Population
JF  - PLoS ONE
N2  - For over a century, the live bearing guppy, Poecilia reticulata, has been used to study sexual selection as well as local adaptation. Natural guppy populations differ in many traits that are of intuitively adaptive significance such as ornamentation, age at maturity, brood size and body shape. Water depth, light supply, food resources and predation regime shape these traits, and barrier waterfalls often separate contrasting environments in the same river. We have assembled and annotated the genome of an inbred single female from a high-predation site in the Guanapo drainage. The final assembly comprises 731.6 Mb with a scaffold N50 of 5.3 MB. Scaffolds were mapped to linkage groups, placing 95% of the genome assembly on the 22 autosomes and the X-chromosome. To investigate genetic variation in the population used for the genome assembly, we sequenced 10 wild caught male individuals. The identified 5 million SNPs correspond to an average nucleotide diversity (π) of 0.0025. The genome assembly and SNP map provide a rich resource for investigating adaptation to different predation regimes. In addition, comparisons with the genomes of other Poeciliid species, which differ greatly in mechanisms of sex determination and maternal resource allocation, as well as comparisons to other teleost genera can begin to reveal how live bearing evolved in teleost fish.
KW  - Trinidadian guppy
KW  - Poecilia reticulata
KW  - genetics
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166755
VL  - 11
IS  - 12
ER  -