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Titel: Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) as a Novel Regulator of Early Astroglial Differentiation
VerfasserIn: Romeo, Ramona
Boden-El Mourabit, Damian
Scheller, Anja
Mark, Melanie D.
Faissner, Andreas
Sprache: Englisch
Titel: Frontiers in Cellular Neuroscience
Bandnummer: 15
Verlag/Plattform: Frontiers
Erscheinungsjahr: 2021
Freie Schlagwörter: astrocyte heterogeneity
differentiation
astrocyte functions
hippocampus
in vivo knockout model
LRP1
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Astrocytes are the most abundant cell type within the central nervous system (CNS) with various functions. Furthermore, astrocytes show a regional and developmental heterogeneity traceable with specific markers. In this study, the influence of the lowdensity lipoprotein receptor-related protein 1 (LRP1) on astrocytic maturation within the hippocampus was analyzed during development. Previous studies mostly focused on the involvement of LRP1 in the neuronal compartment, where the deletion caused hyperactivity and motor dysfunctions in knockout animals. However, the influence of LRP1 on glia cells is less intensively investigated. Therefore, we used a newly generated mouse model, where LRP1 is specifically deleted from GLAST-positive astrocytes colocalized with the expression of the reporter tdTomato to visualize recombination and knockout events in vivo. The influence of LRP1 on the maturation of hippocampal astrocytes was assessed with immunohistochemical stainings against stage-specific markers as well as on mRNA level with RT-PCR analysis. The examination revealed that the knockout induction caused a significantly decreased number of mature astrocytes at an early developmental timepoint compared to control animals. Additionally, the delayed maturation of astrocytes also caused a reduced activity of neurons within the hippocampus. As previous studies showed that the glial specification and maturation of astrocytes is dependent on the signaling cascades Ras/Raf/MEK/Erk and PI3K/Akt, the phosphorylation of the signaling molecules Erk1/2 and Akt was analyzed. The hippocampal tissue of LRP1-deficient animals at P21 showed a significantly decreased amount of activated Erk in comparison to control tissue leading to the conclusion that the activation of this signaling cascade is dependent on LRP1 in astrocytes, which in turn is necessary for proper maturation of astrocytes. Our results showed that the deletion of LRP1 at an early developmental timepoint caused a delayed maturation of astrocytes in the hippocampus based on an altered activation of the Ras/Raf/MEK/Erk signaling pathway. However, with ongoing development these effects were compensated and the number of mature astrocytes was comparable as well as the activity of neurons. Therefore, LRP1 acts as an early regulator of the differentiation and maturation of astrocytes within the hippocampus.
DOI der Erstveröffentlichung: 10.3389/fncel.2021.642521
URL der Erstveröffentlichung: https://www.frontiersin.org/articles/10.3389/fncel.2021.642521
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-395462
hdl:20.500.11880/35642
http://dx.doi.org/10.22028/D291-39546
ISSN: 1662-5102
Datum des Eintrags: 17-Apr-2023
Bezeichnung des in Beziehung stehenden Objekts: Supplementary Material
In Beziehung stehendes Objekt: https://www.frontiersin.org/articles/file/downloadfile/642521_supplementary-materials_images_1_tif/octet-stream/Image%201.TIF/1/642521
https://www.frontiersin.org/articles/file/downloadfile/642521_supplementary-materials_images_2_tif/octet-stream/Image%202.TIF/1/642521
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Physiologie
Professur: M - Prof. Dr. Frank Kirchhoff
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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