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. 2019 Apr 22;44(12):2091–2098. doi: 10.1038/s41386-019-0397-5

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — Brain distribution of tacrine and its hydroxylated metabolites after intraperitoneal administration (10 mg/kg). a, b Sagittal and coronal brain tissue sections imaged by MALDI-MS showing tacrine (m/z 199.123) in 12-w and 14-m mice, respectively (35% of max intensity). c, d Sagittal and coronal brain tissue sections imaged by MALDI-MS showing OH-tacrine (m/z 215.118) in 12-w and 14-m mice, respectively (20% of max intensity). Both analytes were imaged by MALDI-MS at a lateral resolution of 80 μm. e The sagittal and coronal brain tissue sections were subsequently washed and subjected to Nissl staining; brain structures of interest are annotated. Areas used for measuring the Cx/ChP ratio (ratio of a compound’s concentration in the somatosensory cortex to its concentration in the choroid plexus) in the sagittal brain tissue sections are highlighted in red. f Scatter plots of Cx/ChP ratios for tacrine (X-axis) and OH-tacrine (Y-axis) (n = 3). g Bar plot of the whole-brain concentration of tacrine (pmol/mg tissue) and normalized ion intensity of OH-tacrine (n = 4). Statistically significant differences (P < 0.05) are indicated with an asterisk (*). Abbreviations: Acb nucleus accumbens, Cb cerebellum, Cg cingulate cortex, ChP choroid plexus, CPu caudate putamen, Cx cortex, Hip hippocampus, Hyp hypothalamus, LS lateral septal nucleus, M motor cortex, MO medulla oblongata, MS medial septal nucleus, P pons, Pir piriform cortex, S somatocensory cortex, Th thalamus, aca anterior commissure anterior part, cc corpus callosum, f fimbria of the hippocampus, ic internal capsule, 4V fourth ventricle, LV lateral ventricle