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Lithium Accumulates in Neurogenic Brain Regions as Revealed by High Resolution Ion Imaging

Journal article
Authors Giulia Zanni
Wojciech Michno
E. Di Martino
Anna Tjärnlund-Wolf
J. Pettersson
C. E. Mason
G. Hellspong
K. Blomgren
Jörg Hanrieder
Published in Scientific Reports
Volume 7
ISSN 2045-2322
Publication year 2017
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Language en
Keywords nephrogenic diabetes-insipidus, spectrometry tof-sims, human, spinal-cord, mass-spectrometry, vitamin-e, mouse-brain, hippocampal, neurogenesis, adult neurogenesis, gene-expression, rat-brain, Science & Technology - Other Topics, ristensen s, 1985, journal of clinical investigation, v75, p1869
Subject categories Neurosciences


Lithium (Li) is a potent mood stabilizer and displays neuroprotective and neurogenic properties. Despite extensive investigations, the mechanisms of action have not been fully elucidated, especially in the juvenile, developing brain. Here we characterized lithium distribution in the juvenile mouse brain during 28 days of continuous treatment that result in clinically relevant serum concentrations. By using Time-of-Flight Secondary Ion Mass Spectrometry-(ToF-SIMS) based imaging we were able to delineate temporospatial lithium profile throughout the brain and concurrent distribution of endogenous lipids with high chemical specificity and spatial resolution. We found that Li accumulated in neurogenic regions and investigated the effects on hippocampal neurogenesis. Lithium increased proliferation, as judged by Ki67-immunoreactivity, but did not alter the number of doublecortin-positive neuroblasts at the end of the treatment period. Moreover, ToF-SIMS revealed a steady depletion of sphingomyelin in white matter regions during 28d Li-treatment, particularly in the olfactory bulb. In contrast, cortical levels of cholesterol and choline increased over time in Li-treated mice. This is the first study describing ToF-SIMS imaging for probing the brain-wide accumulation of supplemented Li in situ. The findings demonstrate that this technique is a powerful approach for investigating the distribution and effects of neuroprotective agents in the brain.

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