GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Low molecular weight polysialic acid prevents lipopolysaccharide‐induced inflammatory dopaminergic neurodegeneration in humanized SIGLEC11 transgenic mice
    Wiley ; 2021
    In:  Glia Vol. 69, No. 12 ( 2021-12), p. 2845-2862
    Details
    In: Glia, Wiley, Vol. 69, No. 12 ( 2021-12), p. 2845-2862
    Abstract: Parkinson's disease is one of the most common neurodegenerative diseases in the elderly population, with a pathophysiology linked to neuroinflammation, complement activation, and oxidative damage. Soluble polysialic acid with an average degree of polymerization 20 (polySia avDP20) prevents inflammation and oxidative burst in human macrophages via sialic acid‐binding immunoglobulin like lectin‐11 (SIGLEC11) receptor and interferes with alternative complement activation. Here, we confirmed the anti‐inflammatory capacity of polySia avDP20 on cultured murine embryonic stem cell‐derived microglia and analyzed the effect of polySia avDP20 in a lipopolysaccharide‐triggered animal model of Parkinson's disease. We demonstrated a neuroprotective effect of intraperitoneally applied polySia avDP20 in humanized SIGLEC11 transgenic mice after repeated systemic challenge with lipopolysaccharide. Pathway enrichment analysis of the brain transcriptome on day 19 after disease initiation showed that intraperitoneal application of 10 μg/g body weight polySia avDP20 prevented excessive inflammation. In line with these data, polySia avDP20 attenuated the lipopolysaccharide‐triggered increase in mRNA levels of immune‐related genes ( Il1b , Cd14 , Myd88 , Fcer1g , Itgam , C4 , Cybb , Iba1 and Cd68 ) and cell death‐related genes ( Casp8 , Ripk1 and Ripk3 ) in the brains of SIGLEC11 transgenic mice on day 19, but not on day 5. Moreover, immunohistochemistry demonstrated that polySia avDP20 reduced the lipopolysaccharide‐induced increase in immunoreactivity of IBA1 and CD68 in the substantia nigra pars reticulata in SIGLEC11 transgenic and wild type mice on day 19. Furthermore, treatment with polySia avDP20 prevented the loss of dopaminergic neurons in the substantia nigra pars compacta induced by lipopolysaccharide challenge in both SIGLEC11 transgenic and wild type mice on day 19. Thus, our data demonstrate that polySia avDP20 ameliorates inflammatory dopaminergic neurodegeneration and therefore is a promising drug candidate to prevent Parkinson's disease‐related inflammation and neurodegeneration.
    Type of Medium: Online Resource
    ISSN: 0894-1491 , 1098-1136
    URL: Issue
    URL: Article
    DOI: 10.1002/glia.v69.12
    DOI: 10.1002/glia.24073
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 1474828-9
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Reenacting Neuroectodermal Exposure of Hematopoietic Progenitors Enables Scalable Production of Cryopreservable iPSC-Derived Human Microglia
    Springer Science and Business Media LLC ; 2023
    In:  Stem Cell Reviews and Reports Vol. 19, No. 2 ( 2023-02), p. 455-474
    Details
    In: Stem Cell Reviews and Reports, Springer Science and Business Media LLC, Vol. 19, No. 2 ( 2023-02), p. 455-474
    Abstract: Human microglia, as innate immune cells of the central nervous system (CNS), play a central role in the pathogenesis of a large number of neurological and psychiatric disorders. However, experimental access to primary human microglia for biomedical applications such as disease modeling is extremely limited. While induced pluripotent stem cells (iPSCs) could provide an alternative source of microglia, the reenactment of their complex ontogenesis with a yolk sac origin and subsequent priming upon CNS invasion has remained a challenge. Here, we report a developmentally informed in vitro differentiation method for large-scale production and cryopreservation of iPSC-derived microglia (iPSdMiG). Specifically, iPSCs were propagated in conditions yielding both yolk sac hematopoietic derivatives and early neuroepithelial cells. To enable large-scale production, we implemented 3D bioreactor-based dynamic culture conditions and the use of novel mesh macrocarriers. Under these conditions, microglia could be harvested across a time period of at least 6 weeks, with 1 × 10 6 iPSCs giving rise to up to 45 × 10 6 iPSdMiG. The transcriptomic profile of iPSdMiG showed high similarity to adult human microglia, and harvested cells were immunopositive for typical microglial markers. In addition, iPSdMiG were able to secrete pro-inflammatory cytokines, engaged in phagocytotic activity, produced reactive oxygen species and lent themselves to co-culture studies in neural 2D and 3D systems. Importantly, iPSdMiG were efficiently cryopreserved, enabling the establishment of donor-specific microglia cell banks for disease modeling, drug discovery and eventually cell therapy. Graphical abstract Main points. Scalable generation of iPSC-derived multi-lineage embryoid bodies on macrocarriers, reproducibly releasing microglia exhibiting characteristic markers and function. Cells are transcriptomically similar to primary human microglia and cryopreservable.
    Type of Medium: Online Resource
    ISSN: 2629-3269 , 2629-3277
    URL: Article
    DOI: 10.1007/s12015-022-10433-w
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2495579-6
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Phagocytosis‐related NADPH oxidase 2 subunit gp91phox contributes to neurodegeneration after repeated systemic challenge with lipopolysaccharides
    Wiley ; 2021
    In:  Glia Vol. 69, No. 1 ( 2021-01), p. 137-150
    Details
    In: Glia, Wiley, Vol. 69, No. 1 ( 2021-01), p. 137-150
    Abstract: Repeated systemic challenge with lipopolysaccharides (LPS) can induce microglia activation and inflammatory neurodegeneration in the substantia nigra pars compacta region of mice. We now explored the role of mononuclear phagocytes associated nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX‐2) in inflammatory neurodegeneration. Cybb ‐deficient NOX‐2 knock‐out (KO) and control wild type (WT) mice were treated intraperitoneally daily over four consecutive days with 1 μg/gbw/day LPS. Transcriptome analysis by RNA‐seq of total brain tissue indicated increased LPS‐induced upregulation of genes belonging to the reactive oxygen species and reactive nitrogen species production, complement and lysosome activation as well as apoptosis and necroptosis in WT compared to NOX‐2 KO mice. Validation of up‐regulated gene transcripts via qRT‐PCR confirmed that LPS‐challenged NOX‐2 KO mice expressed lower levels of the microglial phagocytosis‐related genes Nos2 , Cd68 , Aif1/Iba1 , Cyba , Itgam , and Fcer1g compared to WT mice at Day 5 after systemic inflammatory challenge, but no significant differences in the pro‐inflammatory genes Tnfα and Il1b as well as microglial IBA1 and CD68 intensities were observed between both genotypes. Furthermore, loss of tyrosine hydroxylase positive (TH+) and NeuN positive neurons in the substantia nigra pars compacta upon repeated systemic LPS application were attenuated in NOX‐2 KO mice. Thus, our data demonstrate that loss of dopaminergic neurons in the substantia nigra pars compacta after repeated systemic challenge with LPS is associated with a microglial phagocytosis‐related gene activation profile involving the NADPH oxidase subunit Cybb/gp91phox.
    Type of Medium: Online Resource
    ISSN: 0894-1491 , 1098-1136
    URL: Issue
    URL: Article
    DOI: 10.1002/glia.v69.1
    DOI: 10.1002/glia.23890
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 1474828-9
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Low molecular weight polysialic acid binds to properdin and reduces the activity of the alternative complement pathway
    Springer Science and Business Media LLC ; 2022
    In:  Scientific Reports Vol. 12, No. 1 ( 2022-04-06)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-04-06)
    Abstract: Sialic acids as the terminal caps of the cellular glycocalyx play an essential role in self-recognition and were shown to modulate complement processes via interaction between α2,3-linked sialic acids and complement factor H. Previously, it was suggested that low molecular weight α2,8-linked polysialic acid (polySia avDP20) interferes with complement activation, but the exact molecular mechanism is still unclear. Here, we show that soluble polySia avDP20 (molecular weight of ~ 6 kDa) reduced the binding of serum-derived alternative pathway complement activator properdin to the cell surface of lesioned Hepa-1c1c7 and PC-12 neuroblastoma cells. Furthermore, polySia avDP20 added to human serum blocked the alternative complement pathway triggered by plate-bound lipopolysaccharides. Interestingly, no inhibitory effect was observed with monosialic acid or oligosialic acid with a chain length of DP3 and DP5. In addition, polySia avDP20 directly bound properdin, but not complement factor H. These data show that soluble polySia avDP20 binds properdin and reduces the alternative complement pathway activity. Results strengthen the previously described concept of self-recognition of sialylation as check-point control of complement activation in innate immunity.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-022-09407-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2615211-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...