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Distribution of CGRP and CGRP receptor in the trigeminovascular system and CNS

Eftekhari, Sajedeh LU (2013) In Lund University Faculty of Medicine Doctoral Dissertation Series 2013:114.
Abstract
Calcitonin gene-related peptide (CGRP) has a key role in the pathophysiology of migraine and is associated with activation of the trigeminovascular system. Recently, CGRP receptor antagonists have been developed with clinical efficacy. The present thesis aimed therefore to investigate the distribution of CGRP and the CGRP receptor in the trigeminovascular system and in parts of the CNS.

In the trigeminal ganglion, CGRP receptor was localized to neurons and satellite glial cells. CGRP was expressed in small/medium-sized neurons, which lacked CGRP receptor. This suggests that if CGRP is released within the ganglion, then intraganglionic CGRP may act on satellite glial cells and on large sized neurons. It was revealed that the... (More)
Calcitonin gene-related peptide (CGRP) has a key role in the pathophysiology of migraine and is associated with activation of the trigeminovascular system. Recently, CGRP receptor antagonists have been developed with clinical efficacy. The present thesis aimed therefore to investigate the distribution of CGRP and the CGRP receptor in the trigeminovascular system and in parts of the CNS.

In the trigeminal ganglion, CGRP receptor was localized to neurons and satellite glial cells. CGRP was expressed in small/medium-sized neurons, which lacked CGRP receptor. This suggests that if CGRP is released within the ganglion, then intraganglionic CGRP may act on satellite glial cells and on large sized neurons. It was revealed that the trigeminal ganglion is not protected by the blood-brain barrier (BBB), suggesting that CGRP receptor antagonists may act here.

In the periphery, expression of CLR and RAMP1 was found in the cranial, meningeal and cerebral arteries, and nerve fibers and rodent mast cells within the dura mater. Indeed we have uncovered that sensory nerves exist in two separate fiber populations and this has not been demonstrated before with such clarity.

In the brainstem we identified certain regions expressing CGRP and its receptor. Brainstem regions, outside BBB, showed CGRP receptor binding, suggesting that CGRP receptor antagonists may act there independently from their ability to pass BBB. Rich expression of CGRP and CGRP receptor was detected in the cerebellum, pointing toward a functional role of CGRP in cerebellum.

This research reveals the expression of CGRP receptor both at peripheral and central sites, implicating that many locations may be involved in migraine pathophysiology (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • MD, Professor Charles, Andrew, Department of Neurology, David Geffen School of Medicine at University of Califorinia, Los Angeles, UCLA.
organization
publishing date
type
Thesis
publication status
published
subject
keywords
CGRP, CLR, RAMP1, migraine, trigeminovascular system, pain, cerebellum
in
Lund University Faculty of Medicine Doctoral Dissertation Series
volume
2013:114
pages
237 pages
publisher
Medicine (Lund)
defense location
Segerfalk lecture hall
defense date
2013-10-01 13:00:00
ISSN
1652-8220
ISBN
978-91-87449-87-1
language
English
LU publication?
yes
id
c5cd387d-8d3c-4027-bebc-6966a0a6a6d2 (old id 4067032)
alternative location
http://dx.doi.org/10.1016/j.neuroscience.2010.05.016
http://cep.sagepub.com/content/30/10/1233.long
http://dx.doi.org/10.1016/j.jpain.2013.03.010
http://www.biomedcentral.com/1471-2202/12/112
http://dx.doi.org/10.1016/j.mcn.2010.10.005
http://link.springer.com/article/10.1007%2Fs12311-013-0509-4
date added to LUP
2016-04-01 14:41:39
date last changed
2019-05-22 04:12:09
@phdthesis{c5cd387d-8d3c-4027-bebc-6966a0a6a6d2,
  abstract     = {Calcitonin gene-related peptide (CGRP) has a key role in the pathophysiology of migraine and is associated with activation of the trigeminovascular system. Recently, CGRP receptor antagonists have been developed with clinical efficacy. The present thesis aimed therefore to investigate the distribution of CGRP and the CGRP receptor in the trigeminovascular system and in parts of the CNS.<br/><br>
In the trigeminal ganglion, CGRP receptor was localized to neurons and satellite glial cells. CGRP was expressed in small/medium-sized neurons, which lacked CGRP receptor. This suggests that if CGRP is released within the ganglion, then intraganglionic CGRP may act on satellite glial cells and on large sized neurons. It was revealed that the trigeminal ganglion is not protected by the blood-brain barrier (BBB), suggesting that CGRP receptor antagonists may act here. <br/><br>
In the periphery, expression of CLR and RAMP1 was found in the cranial, meningeal and cerebral arteries, and nerve fibers and rodent mast cells within the dura mater. Indeed we have uncovered that sensory nerves exist in two separate fiber populations and this has not been demonstrated before with such clarity. <br/><br>
In the brainstem we identified certain regions expressing CGRP and its receptor. Brainstem regions, outside BBB, showed CGRP receptor binding, suggesting that CGRP receptor antagonists may act there independently from their ability to pass BBB. Rich expression of CGRP and CGRP receptor was detected in the cerebellum, pointing toward a functional role of CGRP in cerebellum. <br/><br>
This research reveals the expression of CGRP receptor both at peripheral and central sites, implicating that many locations may be involved in migraine pathophysiology},
  author       = {Eftekhari, Sajedeh},
  isbn         = {978-91-87449-87-1},
  issn         = {1652-8220},
  language     = {eng},
  publisher    = {Medicine (Lund)},
  school       = {Lund University},
  series       = {Lund University Faculty of Medicine Doctoral Dissertation Series},
  title        = {Distribution of CGRP and CGRP receptor in the trigeminovascular system and CNS},
  url          = {http://dx.doi.org/10.1016/j.neuroscience.2010.05.016},
  volume       = {2013:114},
  year         = {2013},
}