Analytical science in neurochemistry

Analytical sciences have played a central role in the development of neuroscience, a field in which molecular measurements of neurotransmitters and other biologically relevant molecules are routinely employed to ask fundamental questions about the brain. Neuroscientists from varied fields commonly use analytical techniques such as electrochemistry, spectroscopy, chromatography and electrophoresis to measure dopamine, serotonin and other neurochemical markers, highlighting the leading role that analytical sciences play in the investigation of the brain. Not surprisingly, therefore, some of the most significant advances in our understanding of neurochemistry have occurred as a function of novel analytical innovations. As such innovations continue in analytical neurochemistry, this themed collection highlights exciting new techniques for the investigation of the brain.

More specifically, this themed collection proposes review articles on fast scan cyclic voltammetry, Raman spectroscopy and imaging mass spectrometry applied to brain molecules, and research articles on new innovations in the fields of electrochemistry, separation science, spectroscopy, nanopore technologies and magnetic resonance imaging (MRI). These articles provide an excellent overview of the status quo of research in analytical neuroscience.

Electrochemistry is a workhorse of analytical neuroscience due to its high sensitivity. The detection of dopamine and serotonin in a short time and with high spatial resolution is now common. While electrochemistry has become the method of choice in the field, it continues to be a very active research field, as highlighted in the critical review on fast-scan cyclic voltammetry (Venton et al., DOI: 10.1039/C9AN01586H). As described in the review, different waveforms, theoretical understanding of the dopamine response, and data analysis have pushed the boundaries of dopamine detection in vivo. An example is provided by Jiao et al., where two phases of dopamine release in the striatum are recorded by amperometry (Jiao et al., DOI: 10.1039/C9AN01941C).

Dopamine has been extensively studied by electrochemistry. Many important aspects of dopamine transmission have thus been unravelled, and electrochemistry is now pushing into other analytes. Li and Ross report a plasma treatment of carbon fibre microelectrodes for the detection of adenosine, ATP, guanosine, and GTP (Li et al., DOI: 10.1039/C9AN01636H). This method improved oxidative currents by up to 6-fold for these purines. Oxygen and ascorbic acid sensing was demonstrated using a cobalt corrole/carbon nanotube electrode and shown to work in the brains of rats (Liu et al., DOI: 10.1039/C9AN01946D). The sensitivity of an enzymatic glutamate sensor has been pushed to near the theoretical limit, guided by mathematical modelling (Huang et al., DOI: 10.1039/C9AN01969C). Electrode construction here included the use of a cross-linked glutamate oxidase layer and a coating of polyphenylenediamine and Nafion. Finally, a sensor capable of dosing melatonin injections in the brain is reported (Castagnola et al., DOI: 10.1039/D0AN00051E).

The combination of microfluidics with electrochemical sensing was shown to detect glucose and lactate changes at high time resolution in the brain following cardiac arrest and resuscitation. Engineering the system with a compact two-channel potentiostat allowed the use of the sensor in the operating theatre (Gowers et al., DOI: 10.1039/C9AN01950B). The combination of microchips with electrophoresis offers the potential for multiplexed catecholamine detection. Progress towards the use of this technology is presented in an article by Gunawardhana et al. (DOI: 10.1039/C9AN01980D). The use of separation methods, such as liquid chromatography with dual electrochemical detection, is reported to determine the tryptophan metabolism (Brooks et al., DOI: 10.1039/C9AN01501A). Capillary electrophoresis coupled to MALDI-MS is reported by DeLaney and Li to improve the coverage of the neuropeptidome of C. borealis (DeLaney et al., DOI: 10.1039/C9AN01883B). The use of imaging MS is reviewed for the detection of gangliosides in healthy and diseased brains (Wang et al., DOI: 10.1039/C9AN02270H).

Spectrophotometric methods are increasingly used for the investigation of neurochemicals. The use of Raman spectroscopy is reviewed by Payne et al. (DOI: 10.1039/D0AN00083C). The potential for using Raman-based spectrophotometric methods for non-invasive sensing inside the brain is reported by Moody et al. (DOI: 10.1039/C9AN01708A). In this paper, they use surface-enhanced spatially-offset Raman spectroscopy (SESORS) to detect a series of neurotransmitters through the skull. Other vibrational spectroscopies, such as IR, can be used to investigate neuropathologies. In an article by Cameron et al. (DOI: 10.1039/C9AN01731C), it was shown that IR can stratify brain tumour patients from serum samples with nearly 90% sensitivity and specificity. In a different realm of application, a DNA-based fluorescence sensor has been developed to investigate arginine-vasopressin, a model neuropeptide (Tan et al., DOI: 10.1039/C9AN02060H).

Other methods are proposed to investigate brain neurochemistry. An aerolysin nanopore sensing scheme is reported for the detection of cysteine, which is involved in aging and neurodegenerative diseases (Yuan et al., DOI: 10.1039/C9AN01965K). MRI is a fundamental tool in clinical diagnostics, especially for neuropathologies. Seo and Clark report the conception of a gadolinium-based MRI agent for tyrosinase (Seo et al., DOI: 10.1039/C9AN02213A). This tool will be highly useful for investigations of the role of tyrosinase in diseases such as Parkinson's disease.

In summary, this collection of papers published in Analyst clearly demonstrates the impact of the vibrant field of analytical neuroscience. The ongoing quest to uncover the role of different molecules in neurochemistry will require new analytical methods to provide fundamental understanding of brain neurochemistry, diagnose neuropathologies and better guide the development of novel therapies. The marriage of analytical science and neuroscience is creating a bright future to advance our understanding of the brain.

Jean-François Masson

Parastoo Hashemi

Martyn G. Boutelle

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