MS imaging and mass spectrometric synaptosome profiling identify PEP-19/pcp4 as a synaptic molecule involved in spatial learning in mice.

The Morris water maze (MWM) spatial learning task has been demonstrated to involve a cognitive switch of action control to serve the transition from an early towards a late learning phase. However, the molecular mechanisms governing this switch are largely unknown. We employed MALDI MS imaging (MSI) to screen for changes in expression of small proteins in brain structures implicated in the different learning phases. We compared mice trained for 3days and 30days in the MWM, reflecting an early and a late learning phase in relation to the acquisition of a spatial learning task. An ion with m/z of 6724, identified as PEP-19/pcp4 by top-down tandem MS, was detected at higher intensity in the dorsal striatum of the late learning phase group compared with the early learning phase group. In addition, mass spectrometric analysis of synaptosomes confirmed the presence of PEP-19/pcp4 at the synapse. PEP-19/pcp4 has previously been identified as a critical determinant of synaptic plasticity in locomotor learning. Our findings extend PEP-19/pcp4 function to spatial learning in the forebrain and put MSI forward as a valid and unbiased research strategy for the discovery and identification of the molecular machinery involved in learning, memory and synaptic plasticity. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.

Direct profiling and identification of peptide expression differences in the pancreas of control and ob/ob mice by imaging mass spectrometry.

Imaging mass spectrometry (IMS) technology utilizes MALDI MS to map molecules of interest in thin tissue sections. In this study, we have evaluated the potential of MALDI IMS to study peptide expression patterns in the mouse pancreas under normal and pathological conditions, and to in situ identify peptides of interest using MS/MS. Different regions of the pancreas of both control and ob/ob mice were imaged, resulting in peptide-specific profiles. The distribution of ions of m/z 3120 and 3439 displayed a striking resemblance with Langerhans islet's histology and, following MS/MS fragmentation and database searching were identified as C-peptide of insulin and glicentin-related polypeptide, respectively. In addition, a significant increase of the 3120 peak intensity in the obese mice was observed. This study underscores the potential of MALDI IMS to study the contribution of peptides to pancreas pathology.

MALDI MS imaging as a tool for biomarker discovery: methodological challenges in a clinical setting.

MALDI MS imaging (MSI) is an analytical tool capable of providing spatial distribution and relative abundance of biomolecules directly in tissue. After 15 years of intense efforts to improve the acquisition and quality of molecular images, MSI has matured into an asset of the proteomic toolbox. The power of MSI lies in the ability to differentiate tissue regions that are not histologically distinct but are characterized by different MS profiles. Recently, MSI has been gaining momentum in biomedical research and has found applications in disease diagnosis and prognosis, biomarker discovery, and drug therapy. Although the technology holds great promise, MSI is still faced with a set of methodological challenges presented by the clinical setting. There is a growing awareness regarding this topic and efforts are being taken to develop clear and practical standards to overcome these challenges. This review presents an overview of MALDI MSI as a biomarker discovery tool and recent methodological progress in the field.