Till sidans topp

Sidansvarig: Webbredaktion
Sidan uppdaterades: 2012-09-11 15:12

Tipsa en vän
Utskriftsversion

Astrocyte-microglial asso… - Göteborgs universitet Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

Astrocyte-microglial association and matrix composition are common events in the natural history of primary familial brain calcification

Artikel i vetenskaplig tidskrift
Författare K. Nahar
T. Lebouvier
M. A. Mae
A. Konzer
J. Bergquist
Y. Zarb
Bengt R Johansson
C. Betsholtz
M. Vanlandewijck
Publicerad i Brain Pathology
ISSN 1015-6305
Publiceringsår 2019
Publicerad vid Institutionen för biomedicin
Språk en
Länkar dx.doi.org/10.1111/bpa.12787
Ämnesord brain calcification, mass spectrometry, PDGFB retention motive knockout, PFBC, Slc20a2 knockout, basal ganglia calcification, pdgf-b, cell-types, gene, expression, mutations, pericytes, mineralization, identification, recruitment, Neurosciences & Neurology, Pathology, velopmental evolution
Ämneskategorier Klinisk medicin

Sammanfattning

Primary familial brain calcification (PFBC) is an age-dependent and rare neurodegenerative disorder characterized by microvascular calcium phosphate deposits in the deep brain regions. Known genetic causes of PFBC include loss-of-function mutations in genes involved in either of three processes-platelet-derived growth factor (PDGF) signaling, phosphate homeostasis or protein glycosylation-with unclear molecular links. To provide insight into the pathogenesis of PFBC, we analyzed murine models of PFBC for the first two of these processes in Pdgfb(ret/ret) and Slc20a2(-/-) mice with regard to the structure, molecular composition, development and distribution of perivascular calcified nodules. Analyses by transmission electron microscopy and immunofluorescence revealed that calcified nodules in both of these models have a multilayered ultrastructure and occur in direct contact with reactive astrocytes and microglia. However, whereas nodules in Pdgfb(ret/ret) mice were large, solitary and smooth surfaced, the nodules in Slc20a2(-/-) mice were multi-lobulated and occurred in clusters. The regional distribution of nodules also differed between the two models. Proteomic analysis and immunofluorescence stainings revealed a common molecular composition of the nodules in the two models, involving proteins implicated in bone homeostasis, but also proteins not previously linked to tissue mineralization. While the brain vasculature of Pdgfb(ret/ret) mice has been reported to display reduced pericyte coverage and abnormal permeability, we found that Slc20a2(-/-) mice have a normal pericyte coverage and no overtly increased permeability. Thus, lack of pericytes and increase in permeability of the blood-brain barrier are likely not the causal triggers for PFBC pathogenesis. Instead, gene expression and spatial correlations suggest that astrocytes are intimately linked to the calcification process in PFBC.

Sidansvarig: Webbredaktion|Sidan uppdaterades: 2012-09-11
Dela:

På Göteborgs universitet använder vi kakor (cookies) för att webbplatsen ska fungera på ett bra sätt för dig. Genom att surfa vidare godkänner du att vi använder kakor.  Vad är kakor?