A metabolomic comparison of mouse models of the Neuronal Ceroid Lipofuscinoses
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 Ī³-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.
- Content Type Journal Article
- Pages 1-10
- DOI 10.1007/s10858-011-9491-7
- Authors
- Reza M. Salek, Department of Biochemistry and the Cambridge Systems Biology Centre, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK
- Michael R. Pears, Department of Biochemistry and the Cambridge Systems Biology Centre, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK
- Jonathan D. Cooper, Pediatric Storage Disorders Laboratory, Department of Neuroscience, Institute of Psychiatry, Kingā??s College London, London, UK
- Hannah M. Mitchison, Department of Paediatrics and Child Health, Royal Free and University College Medical School, London, UK
- David A. Pearce, Department of Pediatrics, Sanford School of Medicine of the University of South Dakota, 2301 East 60th Street North, Sioux Falls, SD 57104-0589, USA
- Russell J. Mortishire-Smith, Johnson & Johnson PR & D, Turnhoutsweg 30, 2340 Beerse, Belgium
- Julian L. Griffin, Department of Biochemistry and the Cambridge Systems Biology Centre, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK
Source: Journal of Biomolecular NMR