New techniques, applications and perspectives in neuropeptide research

Abstract

Neuropeptides are one of the most diverse classes of signaling molecules and have attracted great interest over the years owing to their roles in regulation of a wide range of physiological processes. However, there are unique challenges associated with neuropeptide studies stemming from the highly variable molecular sizes of the peptides, low concentrations, high degree of structural diversity and large number of isoforms. As a result, much effort has been focused on developing new techniques for studying neuropeptides, as well as novel applications directed towards learning more about these endogenous peptides. The areas of importance for neuropeptide studies include structure, localization within tissues, interaction with their receptors, including ion channels, and physiological function. Here, we discuss these aspects and the associated techniques, focusing on technologies that have demonstrated potential in advancing the field in recent years. Most identification and structural information has been gained by mass spectrometry, either alone or with confirmations from other techniques, such as nuclear magnetic resonance spectroscopy and other spectroscopic tools. While mass spectrometry and bioinformatic tools have proven to be the most powerful for large-scale analyses, they still rely heavily on complementary methods for confirmation. Localization within tissues, for example, can be probed by mass spectrometry imaging, immunohistochemistry and radioimmunoassays. Functional information has been gained primarily from behavioral studies coupled with tissue-specific assays, electrophysiology, mass spectrometry and optogenetic tools. Concerning the receptors for neuropeptides, the discovery of ion channels that are directly gated by neuropeptides opens up the possibility of developing a new generation of tools for neuroscience, which could be used to monitor neuropeptide release or to specifically change the membrane potential of neurons. It is expected that future neuropeptide research will involve the integration of complementary bioanalytical technologies and functional assays.

Evolution of neuropeptide signalling systems

“…There is a rich history of research investigating the physiological/behavioural roles of neuropeptides in the animal kingdom, and the article by Jékely et al (2018) highlights some of the key insights that have been obtained. Furthermore, advances in transcriptomics and peptidomics are enabling profiling of neuropeptide expression in identified populations of neurons in multiple species [see review by DeLaney et al (2018) in this issue]. With the availability of such high-resolution data, there are emerging opportunities to explore the evolution of neuropeptide function at multiple levels, from identified neurons to networks of synaptically (and non-synaptically) connected populations of neurons to whole-animal physiology and behaviour.…”

Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics

“…In other words, NDEL1 enzyme activity and its neuropeptide substrates, namely NT and BK, were independently associated with processes involved in SCZ pathophysiology and antipsychotic pharmacotherapy. However, it is still unclear whether alterations in NDEL1 enzyme activity are able to modify the levels of any neuropeptides in vivo, as technical limitations have hindered past efforts 25 . More recently, we have also demonstrated that NDEL1 knockout C. elegans had an important imbalance in the serotonin pathway with significant deficits in their response to typical antipsychotic haloperidol compared to the atypical antipsychotic clozapine, reinforcing the impaired serotonin pathway with NDEL1 expression 24 .…”

The long and the short of it – a perspective on peptidergic regulation of circuits and behaviour

“…The first focuses on, the evolutionary conservation of neuropeptides families (Elphick et al, 2018). The second provides an update on experimental approaches and emerging techniques to dissect peptidergic networks (DeLaney et al, 2018). Further informative reviews on specific neuropeptide families are available elsewhere (e.g.…”