Visualising mouse neuroanatomy and function by metal distribution using laser ablation-inductively coupled plasma-mass spectrometry imaging

Bence Paul; Dominic J. Hare; David P. Bishop; Chad Paton; Van Tran Nguyen; Nerida Cole; Megan M. Niedwiecki; Erica Andreozzi; Angela Vais; Jessica L. Billings; Lisa Bray; Ashley I. Bush; Gawain McColl; Blaine R. Roberts; Paul A. Adlard; David I. Finkelstein; John Hellstrom; Janet M. Hergt; Jon D. Woodhead; Philip A. Doble

doi:10.1039/C5SC02231B

Visualising mouse neuroanatomy and function by metal distribution using laser ablation-inductively coupled plasma-mass spectrometry imaging†

Bence Paul,‡^ab Dominic J. Hare,

‡*^bcd David P. Bishop,^c Chad Paton,^e Van Tran Nguyen,^c Nerida Cole,^c Megan M. Niedwiecki,^d Erica Andreozzi,^b Angela Vais,^b Jessica L. Billings,^b Lisa Bray,^b Ashley I. Bush,

^b Gawain McColl,^b Blaine R. Roberts,^b Paul A. Adlard,^b David I. Finkelstein,^b John Hellstrom,^a Janet M. Hergt,^a Jon D. Woodhead^a and Philip A. Doble*^c

Author affiliations

* Corresponding authors

^a School of Earth Sciences, The University of Melbourne, Parkville, Victoria, Australia

^b The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia

^c Elemental Bio-imaging Facility, University of Technology Sydney, Broadway, New South Wales, Australia
E-mail: dominic.hare@uts.edu.au, philip.doble@uts.edu.au
Tel: +61 2 9512 1792

^d Senator Frank R. Lautenberg Environmental Health Sciences Laboratory, Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA

^e Centre for Star and Planet Formation, Geological Museum, University of Copenhagen, Øster Voldgade 5-7, DK-1350 Copenhagen, Denmark

Abstract

Metals have a number of important roles within the brain. We used laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to map the three-dimensional concentrations and distributions of transition metals, in particular iron (Fe), copper (Cu) and zinc (Zn) within the murine brain. LA-ICP-MS is one of the leading analytical tools for measuring metals in tissue samples. Here, we present a complete data reduction protocol for measuring metals in biological samples, including the application of a pyramidal voxel registration technique to reproducibly align tissue sections. We used gold (Au) nanoparticle and ytterbium (Yb)-tagged tyrosine hydroxylase antibodies to assess the co-localisation of Fe and dopamine throughout the entire mouse brain. We also examined the natural clustering of metal concentrations within the murine brain to elucidate areas of similar composition. This clustering technique uses a mathematical approach to identify multiple ‘elemental clusters’, avoiding user bias and showing that metal composition follows a hierarchical organisation of neuroanatomical structures. This work provides new insight into the distinct compartmentalisation of metals in the brain, and presents new avenues of exploration with regard to region-specific, metal-associated neurodegeneration observed in several chronic neurodegenerative diseases.

Chemical Science

Visualising mouse neuroanatomy and function by metal distribution using laser ablation-inductively coupled plasma-mass spectrometry imaging†

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Visualising mouse neuroanatomy and function by metal distribution using laser ablation-inductively coupled plasma-mass spectrometry imaging

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