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