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Molecular and Cellular Neuroscience
Article . 2011 . Peer-reviewed
License: Elsevier TDM
Data sources: Crossref
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Cerebellar distribution of calcitonin gene-related peptide (CGRP) and its receptor components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) in rat

Authors: Edvinsson, Lars; Eftekhari, Sajedeh; Salvatore, Christopher A; Warfvinge, Karin;

Cerebellar distribution of calcitonin gene-related peptide (CGRP) and its receptor components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) in rat

Abstract

Clinical and experimental results have revealed a fundamental role of calcitonin gene-related peptide (CGRP) in primary headaches. CGRP is widely expressed in neurons both in the central nervous system (CNS) and in peripheral sensory nerves. In the CNS there is a wide distribution of CGRP-containing neurons with the highest levels seen in striatum, amygdale and cerebellum. Moreover, in acute attacks of migraine there is evidence of cerebellar activation. To understand the role of CGRP, antibodies towards the CGRP receptor components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein type 1 (RAMP1) have been developed. In the present study we therefore examined immunohistochemically the distribution of CGRP and its receptor components in the cerebellum. CGRP immunoreactivity was only found intracellularly in the cerebellar Purkinje cell bodies, whereas CLR and RAMP1 were detected on the surface of the Purkinje cell bodies and in their processes. The elaborate dendritic tree of Purkinje cell fibers was distinctly visualized with the RAMP1 antibody. In addition, profoundly stained fibers spanning from the molecular layer into the medulla was observed with the RAMP1 antibody. Judged from the high density of immunoreactive cells expressing CGRP, RAMP1 or CLR, and from the double staining of CGRP and RAMP1 it is likely that most, if not all, Purkinje cells express both the peptide and the receptor components. Double staining with RAMP1 and the glial cell markers glial fibrillary acidic protein (GFAP) and S-100 revealed an almost identical staining pattern of the antibodies in the area of the cell body surfaces. However, as judged by confocal microscopy, no double staining was present. Instead, it was discovered that the glial cells tightly surrounded the Purkinje cells which easily could be interpreted as co-localization in the epifluorescence microscope. Our observations demonstrate that there is a rich expression of CGRP and CGRP receptor elements in the cerebellum which points towards a functional role of CGRP in cerebellar Purkinje cells. Recent advances in the biology of the cerebellum indicate that there may be a role in nociception; hence a target of the recently discovered CGRP receptor antagonists that have demonstrated improvement in migraine pain and associated symptoms could be cerebellar CGRP receptors.

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Keywords

Calcitonin Gene-Related Peptide, Migraine Disorders, Calcitonin Receptor-Like Protein, Rats, Receptor Activity-Modifying Protein 1, Purkinje Cells, Other Clinical Medicine, Cerebellum, Animals, Humans, Receptors, Calcitonin Gene-Related Peptide

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    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    82
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
82
Top 10%
Top 10%
Top 10%
Green
bronze