caa a22 4500 445324880 CHVBK 20180317142717.0 cr unu---uuuuu 170323e20110401xx s 000 0 eng 10.1007/s10858-011-9491-7 doi (NATIONALLICENCE)springer-10.1007/s10858-011-9491-7 A metabolomic comparison of mouse models of the Neuronal Ceroid Lipofuscinoses [Elektronische Daten] [Reza Salek, Michael Pears, Jonathan Cooper, Hannah Mitchison, David Pearce, Russell Mortishire-Smith, Julian Griffin] 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 (6month) Cln3 mice, where the disease is relatively advanced, while the metabolism of nclf mice was more akin to younger (1-2months) 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. Springer Science+Business Media B.V., 2011 Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) nationallicence Batten disease nationallicence CLN3 nationallicence NMR nationallicence Metabolomics nationallicence Neurodegeneration nationallicence Salek Reza Department of Biochemistry and the Cambridge Systems Biology Centre, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK aut Pears Michael Department of Biochemistry and the Cambridge Systems Biology Centre, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK aut Cooper Jonathan Pediatric Storage Disorders Laboratory, Department of Neuroscience, Institute of Psychiatry, King's College London, London, UK aut Mitchison Hannah Department of Paediatrics and Child Health, Royal Free and University College Medical School, London, UK aut Pearce David Department of Pediatrics, Sanford School of Medicine of the University of South Dakota, 2301 East 60th Street North, 57104-0589, Sioux Falls, SD, USA aut Mortishire-Smith Russell Johnson & Johnson PR & D, Turnhoutsweg 30, 2340, Beerse, Belgium aut Griffin Julian Department of Biochemistry and the Cambridge Systems Biology Centre, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK aut Journal of Biomolecular NMR Springer Netherlands 49/3-4(2011-04-01), 175-184 0925-2738 49:3-4<175 2011 49 10858 https://doi.org/10.1007/s10858-011-9491-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10858-011-9491-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Salek Reza Department of Biochemistry and the Cambridge Systems Biology Centre, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK aut NATIONALLICENCE 700 1- Pears Michael Department of Biochemistry and the Cambridge Systems Biology Centre, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK aut NATIONALLICENCE 700 1- Cooper Jonathan Pediatric Storage Disorders Laboratory, Department of Neuroscience, Institute of Psychiatry, King's College London, London, UK aut NATIONALLICENCE 700 1- Mitchison Hannah Department of Paediatrics and Child Health, Royal Free and University College Medical School, London, UK aut NATIONALLICENCE 700 1- Pearce David Department of Pediatrics, Sanford School of Medicine of the University of South Dakota, 2301 East 60th Street North, 57104-0589, Sioux Falls, SD, USA aut NATIONALLICENCE 700 1- Mortishire-Smith Russell Johnson & Johnson PR & D, Turnhoutsweg 30, 2340, Beerse, Belgium aut NATIONALLICENCE 700 1- Griffin Julian Department of Biochemistry and the Cambridge Systems Biology Centre, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK aut NATIONALLICENCE 773 0- Journal of Biomolecular NMR Springer Netherlands 49/3-4(2011-04-01), 175-184 0925-2738 49:3-4<175 2011 49 10858 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer