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004-Mass Spec-V17

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The Diverse Applications of <strong>Mass</strong> <strong>Spec</strong>trometry<br />

Measuring<br />

How the Brain<br />

Metabolizes in<br />

Real-time<br />

Adam Tozer, PhD<br />

Previously, if you wanted to analyze brain metabolites<br />

over time in a mouse study, you would need to extract<br />

brains from different mice at different time points. An<br />

‘upside’ to this method is that metabolite changes could be<br />

measured from whole areas of the brain. However, the data only<br />

provided a snapshot of the metabolic changes at distinct time<br />

points. Previously, it was not possible to view metabolic changes<br />

happening in real-time. Ground-breaking work included<br />

the development of checkpoint blockade therapy, 5 targeting<br />

cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) 6<br />

and programmed death receptor-1 (PD-1) 7 with monoclonal<br />

antibodies in tumors. Many patients treated with these new<br />

therapies had tumor remissions which has raised the prospect<br />

that some of these cancers may be manageable as chronic<br />

conditions.<br />

An innovative approach developed by Assistant Professor Kei<br />

Zaitsu and Lecturer Yumi Hayashi at Nagoya University, Japan,<br />

enables the real-time monitoring of brain cell metabolism in<br />

anaesthetized animals.<br />

Needle-sharp Sampling and Identification<br />

The team previously showed that the new system could be used<br />

to monitor metabolomic changes in the liver 1 of anaesthetized<br />

rats in real-time, so next wanted to try the system on the brain.<br />

Technology Networks 2018<br />

15<br />

Figure 1: Differences between conventional metabolome analysis for dissected brain<br />

samples and the newly developed in vivo real-time monitoring system. Conventional<br />

metabolome analysis for dissected brain samples is widely accepted as a general<br />

protocol, though there is a critical issue: the effect of death on metabolome cannot<br />

be avoided. However, the newly developed in vivo real-time monitoring system<br />

can observe metabolic dynamics without the effect of death and there are high<br />

expectations for it to reveal hidden mechanisms. The system will also provide a novel<br />

visualization technique for homeostasis, which can be applied in healthcare risk<br />

management. Credit: Kei Zaitsu<br />

By combining an acupuncture needle as an ionization device<br />

with sensitive mass spectrometry machinery, the team<br />

successfully monitored eight cerebrum metabolites related to<br />

central energy metabolism at 20 second intervals for three hours,<br />

in anaesthetized mice. The findings are published in the journal<br />

Analytical Chemistry. 2<br />

TechnologyNetworks.com

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