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Lithium Accumulates in Neurogenic Brain Regions as Revealed by High Resolution Ion Imaging
Karolinska Univ Hosp, Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Ctr Brain Repair & Rehabil, Inst Neurosci & Physiol, Gothenburg, Sweden..
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden..
Karolinska Univ Hosp, Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
Univ Gothenburg, Sahlgrenska Acad, Ctr Brain Repair & Rehabil, Inst Neurosci & Physiol, Gothenburg, Sweden..
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 40726Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2017. Vol. 7, article id 40726
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Analytical Chemistry Cancer and Oncology Neurology Pediatrics
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URN: urn:nbn:se:uu:diva-316029DOI: 10.1038/srep40726ISI: 000392273300001PubMedID: 28098178OAI: oai:DiVA.org:uu-316029DiVA, id: diva2:1076914
Funder
Swedish Research CouncilSwedish Childhood Cancer FoundationSwedish Cancer SocietySwedish Radiation Safety AuthorityThe Dementia Association - The National Association for the Rights of the Demented
Available from: 2017-02-24 Created: 2017-02-24 Last updated: 2017-11-29Bibliographically approved

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