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Direct visualization of an antidepressant analog using surface-enhanced Raman scattering in the brain
Masato Tanuma, … , Katsumasa Fujita, Hitoshi Hashimoto
Masato Tanuma, … , Katsumasa Fujita, Hitoshi Hashimoto
Published March 3, 2020
Citation Information: JCI Insight. 2020;5(6):e133348. https://doi.org/10.1172/jci.insight.133348.
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Resource and Technical Advance Neuroscience

Direct visualization of an antidepressant analog using surface-enhanced Raman scattering in the brain

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Abstract

Detailed spatial information of low–molecular weight compound distribution, especially in the brain, is crucial to understanding their mechanism of actions. Imaging techniques that can directly visualize drugs in the brain at a high resolution will complement existing tools for drug distribution analysis. Here, we performed surface-enhanced Raman scattering (SERS) imaging using a bioorthogonal alkyne tag to visualize drugs directly in situ at a high resolution. Focusing on the selective serotonin reuptake inhibitor S-citalopram (S-Cit), which possesses a nitrile group, we substituted an alkynyl group into its structure and synthesized alkynylated S-Cit (Alk-S-Cit). The brain transitivity and the serotonin reuptake inhibition of Alk-S-Cit were not significantly different as compared with S-Cit. Alk-S-Cit was visualized in the coronal mouse brain section using SERS imaging with silver nanoparticles. Furthermore, SERS imaging combined with fluorescence microscopy allowed Alk-S-Cit to be visualized in the adjacent neuronal membranes, as well as in the brain vessel and parenchyma. Therefore, our multimodal imaging technique is an effective method for detecting low–molecular weight compounds in their original tissue environment and can potentially offer additional information regarding the precise spatial distribution of such drugs.

Authors

Masato Tanuma, Atsushi Kasai, Kazuki Bando, Naoyuki Kotoku, Kazuo Harada, Masafumi Minoshima, Kosuke Higashino, Atsushi Kimishima, Masayoshi Arai, Yukio Ago, Kaoru Seiriki, Kazuya Kikuchi, Satoshi Kawata, Katsumasa Fujita, Hitoshi Hashimoto

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Figure 4

SERS imaging of Alk-S-Cit.

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SERS imaging of Alk-S-Cit.
(A) Alk-S-Cit solution with concentration of ...
(A) Alk-S-Cit solution with concentration of 40 μM and exposure time of 2 seconds was used for measurements of spontaneous Raman spectra, while sample solution with a concentration of 40 μM and exposure time of 200 ms were used for SERS measurements. The excitation wavelength was 532 nm and laser power was 0.4 mW/μm2 on sample plane. (B) SERS intensity map at 2170 cm–1 for different concentrations of Alk-S-Cit (1 nM to 10 μM) and S-Cit (10 μM) measured on glass substrates with dispersed Ag nanoparticles (φ = 23 nm). The excitation wavelength was 532 nm and laser power was 0.4 mW/μm2 on sample plane. Scale bar: 10 μm. (C) Probability distributions of SERS intensity for various concentrations of Alk-S-Cit (1 nM to 10 μM) are shown as comparative histograms. (D–F) Representative images of bright-field (D), heatmap of SERS signal of fingerprint region (averaged over 500–1500 cm–1) (E), and Alk-S-Cit (averaged over 2141–2180 cm–1) (F) in the same field of view. Scale bar: 10 μm. (G) Spectrums a–f show SERS spectra at positions shown in F, and spectrum g shows average of these spectra. Each SERS peak (cm–1) is shown in G.

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