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Identification and quantification of neuropeptides in naive mouse spinal cord using mass spectrometry reveals [des-Ser1]-cerebellin as a novel modulator of nociception
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
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2014 (English)In: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 130, no 2, 199-214 p.Article in journal (Refereed) Published
Abstract [en]

Neuropeptide transmitters involved in nociceptive processes are more likely to be expressed in the dorsal than the ventral horn of the spinal cord. This study was designed to examine the relative distribution of neuropeptides between the dorsal and ventral spinal cord in naive mice using liquid chromatography, high-resolution mass spectrometry. We identified and relatively quantified 36 well-characterized full-length neuropeptides and an additional 168 not previously characterized peptides. By extraction with organic solvents we identified seven additional full-length neuropeptides. The peptide [des-Ser1]-cerebellin (desCER), originating from cerebellin precursor protein 1 (CBLN1), was predominantly expressed in the dorsal horn. Immunohistochemistry showed the presence of CBLN1 immunoreactivity with a punctate cytoplasmic pattern in neuronal cell bodies throughout the spinal gray matter. The signal was stronger in the dorsal compared to the ventral horn, with most CBLN1 positive cells present in outer laminae II/III, colocalizing with calbindin, a marker for excitatory interneurons. Intrathecal injection of desCER induced a dose-dependent mechanical hypersensitivity but not heat or cold hypersensitivity. This study provides evidence for involvement of desCER in nociception and provides a platform for continued exploration of involvement of novel neuropeptides in the regulation of nociceptive transmission.

Place, publisher, year, edition, pages
2014. Vol. 130, no 2, 199-214 p.
Keyword [en]
mass spectrometry, neuropeptides, nociception, pain, peptidomics, spinal cord
National Category
Medical Biotechnology Neurosciences Basic Medicine
URN: urn:nbn:se:uu:diva-230511DOI: 10.1111/jnc.12730ISI: 000339283200005OAI: oai:DiVA.org:uu-230511DiVA: diva2:744476
Available from: 2014-09-08 Created: 2014-08-26 Last updated: 2014-09-08Bibliographically approved

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