Ossified blood vessels in primary familial brain calcification elicit a neurotoxic astrocyte response

Brain : a Journal of Neurology
Yvette ZarbAnnika Keller

Abstract

Brain calcifications are commonly detected in aged individuals and accompany numerous brain diseases, but their functional importance is not understood. In cases of primary familial brain calcification, an autosomally inherited neuropsychiatric disorder, the presence of bilateral brain calcifications in the absence of secondary causes of brain calcification is a diagnostic criterion. To date, mutations in five genes including solute carrier 20 member 2 (SLC20A2), xenotropic and polytropic retrovirus receptor 1 (XPR1), myogenesis regulating glycosidase (MYORG), platelet-derived growth factor B (PDGFB) and platelet-derived growth factor receptor β (PDGFRB), are considered causal. Previously, we have reported that mutations in PDGFB in humans are associated with primary familial brain calcification, and mice hypomorphic for PDGFB (Pdgfbret/ret) present with brain vessel calcifications in the deep regions of the brain that increase with age, mimicking the pathology observed in human mutation carriers. In this study, we characterize the cellular environment surrounding calcifications in Pdgfbret/ret animals and show that cells around vessel-associated calcifications express markers for osteoblasts, osteoclasts and osteocytes, and th...Continue Reading

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Citations

Jun 4, 2019·Current Opinion in Neurology·Ana WestenbergerChristine Klein
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Methods Mentioned

BETA
biopsies

Software Mentioned

GraphPad
EthoVision
Imaris
ImageJ
MAPshim
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Fiji
Paravision
Prism7

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