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Journal of Inherited Metabolic Disease

, Volume 37, Issue 1, pp 83–92 | Cite as

Human and mouse neuroinflammation markers in Niemann-Pick disease, type C1

  • Stephanie M. Cologna
  • Celine V. M. Cluzeau
  • Nicole M. Yanjanin
  • Paul S. Blank
  • Michelle K. Dail
  • Stephan Siebel
  • Cynthia L. Toth
  • Christopher A. Wassif
  • Andrew P. Lieberman
  • Forbes D. Porter
Original Article

Abstract

Niemann-Pick disease, type C1 (NPC1) is an autosomal recessive lipid storage disorder in which a pathological cascade, including neuroinflammation occurs. While data demonstrating neuroinflammation is prevalent in mouse models, data from NPC1 patients is lacking. The current study focuses on identifying potential markers of neuroinflammation in NPC1 from both the Npc1 mouse model and NPC1 patients. We identified in the mouse model significant changes in expression of genes associated with inflammation and compared these results to the pattern of expression in human cortex and cerebellar tissue. From gene expression array analysis, complement 3 (C3) was increased in mouse and human post-mortem NPC1 brain tissues. We also characterized protein levels of inflammatory markers in cerebrospinal fluid (CSF) from NPC1 patients and controls. We found increased levels of interleukin 3, chemokine (C-X-C motif) ligand 5, interleukin 16 and chemokine ligand 3 (CCL3), and decreased levels of interleukin 4, 10, 13 and 12p40 in CSF from NPC1 patients. CSF markers were evaluated with respect to phenotypic severity. Miglustat treatment in NPC1 patients slightly decreased IL-3, IL-10 and IL-13 CSF levels; however, further studies are needed to establish a strong effect of miglustat on inflammation markers. The identification of inflammatory markers with altered levels in the cerebrospinal fluid of NPC1 patients may provide a means to follow secondary events in NPC1 disease during therapeutic trials.

Keywords

NPC1 Patient Miglustat Cerebellar Tissue Sandhoff Disease Post Birth 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

Human tissue was obtained from the NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore, MD. This study was supported by the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by the National Institute of Neurological Disorders and Stroke (R01 NS063967 to APL). Support for this work was also provided by Bench-to-Bedside awards from the NIH Clinical Center and Office of Rare Diseases. Research was supported in part by a grant from the National Niemann-Pick Disease Foundation to SMC. NMY was supported by the Ara Parseghian Medical Research Foundation (APMRF). APMRF also supported the collection of control CSF samples which were facilitated by the efforts of Dr. Cyndi Tifft. The authors would also like to acknowledge the contribution of the caretakers, the patients and their families, who participated in this study.

Conflict of interest

None

Supplementary material

10545_2013_9610_MOESM1_ESM.docx (8.7 mb)
ESM 1 (DOCX 8.72 mb)
10545_2013_9610_MOESM2_ESM.xlsx (32 kb)
ESM 2 (XLSX 32 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg (outside the USA) 2013

Authors and Affiliations

  • Stephanie M. Cologna
    • 1
  • Celine V. M. Cluzeau
    • 1
  • Nicole M. Yanjanin
    • 1
  • Paul S. Blank
    • 2
  • Michelle K. Dail
    • 1
  • Stephan Siebel
    • 1
  • Cynthia L. Toth
    • 1
  • Christopher A. Wassif
    • 1
  • Andrew P. Lieberman
    • 3
  • Forbes D. Porter
    • 1
  1. 1.Program in Developmental Endocrinology and Genetics, Section on Molecular DysmorphologyNICHD, NIH, DHHSBethesdaUSA
  2. 2.Program in Physical Biology, Section on Membrane & Cellular BiophysicsNICHD, NIH, DHHSBethesdaUSA
  3. 3.Department of PathologyUniversity of MichiganAnn ArborUSA

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