Journal of Biomolecular NMR

, Volume 49, Issue 3, pp 175–184

A metabolomic comparison of mouse models of the Neuronal Ceroid Lipofuscinoses

Authors

  • Reza M. Salek
    • Department of Biochemistry and the Cambridge Systems Biology CentreUniversity of Cambridge
  • Michael R. Pears
    • Department of Biochemistry and the Cambridge Systems Biology CentreUniversity of Cambridge
  • Jonathan D. Cooper
    • Pediatric Storage Disorders Laboratory, Department of Neuroscience, Institute of PsychiatryKing’s College London
  • Hannah M. Mitchison
    • Department of Paediatrics and Child HealthRoyal Free and University College Medical School
  • David A. Pearce
    • Department of PediatricsSanford School of Medicine of the University of South Dakota
  • Russell J. Mortishire-Smith
    • Johnson & Johnson PR & D
    • Department of Biochemistry and the Cambridge Systems Biology CentreUniversity of Cambridge
    • Department of BiochemistryUniversity of Cambridge
Article

DOI: 10.1007/s10858-011-9491-7

Cite this article as:
Salek, R.M., Pears, M.R., Cooper, J.D. et al. J Biomol NMR (2011) 49: 175. doi:10.1007/s10858-011-9491-7

Abstract

The Neuronal Ceroid Lipofuscinoses (NCL) are a group of fatal inherited neurodegenerative diseases in humans distinguished by a common clinical pathology, characterized by the accumulation of storage body material in cells and gross brain atrophy. In this study, metabolic changes in three NCL mouse models were examined looking for pathways correlated with neurodegeneration. Two mouse models; motor neuron degeneration (mnd) mouse and a variant model of late infantile NCL, termed the neuronal ceroid lipofuscinosis (nclf) mouse were investigated experimentally. Both models exhibit a characteristic accumulation of autofluorescent lipopigment in neuronal and non neuronal cells. The NMR profiles derived from extracts of the cortex and cerebellum from mnd and nclf mice were distinguished according to disease/wildtype status. In particular, a perturbation in glutamine and glutamate metabolism, and a decrease in γ-amino butyric acid (GABA) in the cerebellum and cortices of mnd (adolescent mice) and nclf mice relative to wildtype at all ages were detected. Our results were compared to the Cln3 mouse model of NCL. The metabolism of mnd mice resembled older (6 month) Cln3 mice, where the disease is relatively advanced, while the metabolism of nclf mice was more akin to younger (1-2 months) Cln3 mice, where the disease is in its early stages of progression. Overall, our results allowed the identification of metabolic traits common to all NCL subtypes for the three animal models.

Keywords

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) Batten disease CLN3 NMR Metabolomics Neurodegeneration

Copyright information

© Springer Science+Business Media B.V. 2011