PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Bres, E.E.* ; Safina, D.* ; Müller, J.* ; Bedner, P.* ; Yang, H.* ; Helluy, X.* ; Shchyglo, O.* ; Jansen, S.* ; Mark, M.D.* ; Esser, A.* ; Steinhäuser, C.* ; Herlitze, S.* ; Pietrzik, C.U.* ; Sirko, S. ; Manahan-Vaughan, D.* ; Faissner, A.*

Lipoprotein receptor loss in forebrain radial glia results in neurological deficits and severe seizures.

Glia 68, 2517-2549 (2020)
Research data DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
The Alzheimer disease-associated multifunctional low-density lipoprotein receptor-related protein-1 is expressed in the brain. Recent studies uncovered a role of this receptor for the appropriate functioning of neural stem cells, oligodendrocytes, and neurons. The constitutive knock-out (KO) of the receptor is embryonically lethal. To unravel the receptors' role in the developing brain we generated a mouse mutant by specifically targeting radial glia stem cells of the dorsal telencephalon. The low-density lipoprotein receptor-related protein-1 lineage-restricted KO female and male mice, in contrast to available models, developed a severe neurological phenotype with generalized seizures during early postnatal development. The mechanism leading to a buildup of hyperexcitability and emergence of seizures was traced to a failure in adequate astrocyte development and deteriorated postsynaptic density integrity. The detected impairments in the astrocytic lineage: precocious maturation, reactive gliosis, abolished tissue plasminogen activator uptake, and loss of functionality emphasize the importance of this glial cell type for synaptic signaling in the developing brain. Together, the obtained results highlight the relevance of astrocytic low-density lipoprotein receptor-related protein-1 for glutamatergic signaling in the context of neuron-glia interactions and stage this receptor as a contributing factor for epilepsy.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
5.984
1.329
4
2
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Astrocytes ; Epilepsy ; Lipoprotein Receptor-related Protein ; Radial Glia Stem Cells ; Reactive Astrocytes ; Seizures ; Tissue Plasminogen Activator; Methyl-d-aspartate; Tissue-plasminogen Activator; Immediate-early Gene; Conditional Deletion; Glutamate Uptake; Protein-1 Lrp1; Mouse Model; Brain; Expression; Astrocytes
Language english
Publication Year 2020
HGF-reported in Year 2020
ISSN (print) / ISBN 0894-1491
e-ISSN 1098-1136
Journal Glia
Quellenangaben Volume: 68, Issue: 12, Pages: 2517-2549 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa
Reviewing status Peer reviewed
Institute(s) Institute of Stem Cell Research (ISF)
POF-Topic(s) 30204 - Cell Programming and Repair
Research field(s) Stem Cell and Neuroscience
PSP Element(s) G-500800-001
DOI 10.1002/glia.23869
WOS ID WOS:000542421900001
Scopus ID 85087308158
Scopus ID 85087016064
PubMed ID 32579270
Erfassungsdatum 2020-07-03
[➜Report correction]