Abstract
Data of mice with PDGF-B-truncating mutation (Pdgfb ret/ret) from different research groups indicate that the malfunction of this protein leads to reduced pericyte recruitment, loss of Blood-Brain Barrier (BBB) integrity and bilateral brain calcification. This makes these mice important models for Primary Brain Calcification and pericyte-BBB correlation studies. The global brain pericyte count is reduced in Pdgfb ret/ret mice, with higher BBB permeability. We have overlapped the data from other research groups into a figure to further analyze the findings. Calcifications form within midbrain, interbrain, basal forebrain, and pons. Interestingly, these calcification-prone regions have a comparably higher pericyte count and lower BBB leakage in relation to other non-calcifying regions of the Pdgfb ret/ret mouse (such as the cortex and striatum). A comparatively higher BBB integrity in regions prone to calcification seems paradoxical and indicates that other region-specific changes are the cause of the calcifications.
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References
Armulik A, Genove G, Mae M, Nisancioglu MH, Wallgard E, Niaudet C et al (2010) Pericytes regulate the blood-brain barrier. Nature 468:557–561
Batla A, Tai XY, Schottlaender L, Erro R, Balint B, Bhatia KP (2017) Deconstructing Fahr’s disease/syndrome of brain calcification in the era of new genes. Parkinsonism Relat Disord 37:1–10
Bjarnegard M, Enge M, Norlin J, Gustafsdottir S, Fredriksson S, Abramsson A et al (2004) Endothelium-specific ablation of PDGFB leads to pericyte loss and glomerular, cardiac and placental abnormalities. Development 131:1847–1857
Enge M, Bjarnegard M, Gerhardt H, Gustafsson E, Kalen M, Asker N et al (2002) Endothelium-specific platelet-derived growth factor-B ablation mimics diabetic retinopathy. EMBO J 21:4307–4316
Hayashi T, Legati A, Nishikawa T, Coppola G (2015) First Japanese family with primary familial brain calcification due to a mutation in the PDGFB gene: an exome analysis study. Psychiatry Clin Neurosci 69:77–83
Keller A, Westenberger A, Sobrido MJ, Garcia-Murias M, Domingo A, Sears RL et al (2013) Mutations in the gene encoding PDGF-B cause brain calcifications in humans and mice. Nat Genet 45:1077–1082
Legati A, Giovannini D, Nicolas G, Lopez-Sanchez U, Quintans B, Oliveira JRM et al (2015) Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export. Nat Genet 47:579–581
Lein ES, Hawrylycz MJ, Ao N, Ayres M, Bensinger A, Bernard A et al (2007) Genome-wide atlas of gene expression in the adult mouse brain. Nature 445:168–176
Miklossy J, Mackenzie IR, Dorovini-Zis K, Calne DB, Wszolek ZK, Klegeris A et al (2005) Severe vascular disturbance in a case of familial brain calcinosis. Acta Neuropathol 109:643–653
Nicolas G, Pottier C, Maltete D, Coutant S, Rovelet-Lecrux A, Legallic S et al (2013) Mutation of the PDGFRB gene as a cause of idiopathic basal ganglia calcification. Neurology 80:181–187
Nicolas G, Charbonnier C, de Lemos RR, Richard A-C, Guillin O, Wallon D et al (2015) Brain calcification process and phenotypes according to age and sex: Lessons from SLC20A2, PDGFB, and PDGFRB mutation carriers. Am J Med Genet B Neuropsychiatr Genet 168:586–594
Vanlandewijck M, Lebouvier T, Andaloussi Mae M, Nahar K, Hornemann S, Kenkel D et al (2015) Functional characterization of germline mutations in PDGFB and PDGFRB in primary familial brain calcification. PLoS One 10:e0143407
Villaseñor R, Kuennecke B, Ozmen L, Ammann M, Kugler C, Gruninger F et al. (2017) Region-specific permeability of the blood-brain barrier upon pericyte loss. J Cereb Blood Flow Metab 271678X17697340
Wallingford MC, Chia JJ, Leaf EM, Borgeia S, Chavkin NW, Sawangmake C et al (2017) SLC20A2 deficiency in mice leads to elevated phosphate levels in cerbrospinal fluid and glymphatic pathway-associated arteriolar calcification, and recapitulates human idiopathic basal ganglia calcification. Brain Pathol 27:64–76
Wang C, Li Y, Shi L, Ren J, Patti M, Wang T et al (2012) Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis. Nat Genet 44:254–256
Acknowledgements
The authors would like to thank the following funding agencies for their financial support: Fundação de Amparo a Ciência e Tecnologia - FACEPE (Award IBPG-0897-2.02/15), Conselho Nacional CNPq (Award 310150/2016-7) and CAPES (Award 8887.131374/2016-00).
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Moura, D.A.P., Lemos, R.R. & Oliveira, J.R.M. New Data from Pdfgb ret/ret Mutant Mice Might Lead to a Paradoxical Association Between Brain Calcification, Pericytes Recruitment and BBB Integrity. J Mol Neurosci 63, 419–421 (2017). https://doi.org/10.1007/s12031-017-0992-z
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DOI: https://doi.org/10.1007/s12031-017-0992-z