Journal article
Longitudinal spatial mapping of lipid metabolites reveals pre-symptomatic changes in the hippocampi of Huntington's disease transgenic mice
F Farzana, M McConville, T Renoir, S Li, S Nie, H Tran, AJ Hannan, DM Hatters, BA Boughton
Neurobiology of Disease | Published : 2023
Abstract
In Huntington's disease (HD), a key pathological feature includes the development of inclusion-bodies of fragments of the mutant huntingtin protein in the neurons of the striatum and hippocampus. To examine the molecular changes associated with inclusion-body formation, we applied MALDI-mass spectrometry imaging and deuterium pulse labelling to determine lipid levels and synthesis rates in the hippocampus of a transgenic mouse model of HD (R6/1 line). The R6/1 HD mice lacked inclusions in the hippocampus at 6 weeks of age (pre-symptomatic), whereas inclusions were pervasive by 16 weeks of age (symptomatic). Hippocampal subfields (CA1, CA3 and DG), which formed the highest density of inclusio..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
We thank Federico Martinez-Seidel from Max Planck Institute of Molecular Plant Physiology, Germany for his technical help with the development of KineticMSI, an R-based data analysis pipeline. We also thank the Melbourne Mass Spectrometry and Proteomics Facility of The Bio21 Molecular Science and Biotechnology Institute and Metabolomics Australia at The University of Melbourne for mass spectrometry anal-ysis. We also acknowledge the contribution of Melbourne Statistical Consulting Platform, University of Melbourne for their assistance with data analysis. For technical support with histology staining, we would like to thank Dr. Ian Birchall from the Histology and Neuropathology scientific services, Florey Institute of Neuroscience and Mental Health. This work was supported by National Health and Medical Research Council (NHMRC) through the Ideas Grant ID APP1184166 awarded to D Hatters, BA Boughton. D Hatters is an NHMRC Senior Research Fellow and AJ Hannan is an NHMRC Principal Research Fellow. The generation of the HD and WT mouse tissues was supported by Project Grant ID APP1124356 awarded to T Renoir and AJ Hannan. All authors contributed to the article and approved the final submitted version.