質量分析によるモノアミンの局在と、その動態のin situイメージング

抄録

Due to recent technical advances in instrumentation and sample preparation protocols, current imaging mass spectrometry (IMS) is now able to visualize the localization of neurotransmitters, including monoamines. Although monoamine-producing neurons, as well as their projections and synapses, have been thoroughly characterized, localization and fluctuation of monoamines within these circuits remains unclear. We addressed this problem with generation of the in situ monoamine concentration maps obtained with IMS, which allow us to study fluctuations in local monoamine concentration in response to physiological stimuli, drug administration, and neurodegenerative disease progression. Our recent studies have shown that monoamines accumulate not only in cell bodies expressing enzymes that produce these transmitters (such as TH and TPH), but also in distant nerve terminals. This indicates that they are either actively transported along the axon or synthesized locally at the terminals. Furthermore, since the pharmacokinetics of exogenous drugs can also be visualized with IMS, the development of a method for simultaneous imaging of selective serotonin reuptake inhibitors (SSRIs) and monoamines could reveal where long-term SSRIs accumulate and how they affect local monoamine metabolism. I'll also show that how the stimulated immune metabolism alters brain monoamine signaling, by visualization of deficiency of the serotonin and dopamine in the brain, resulting in behavioral changes.