CamKIIα and VPAC1 Expressions in the Caudal Trigeminal Nucleus of Rats After Systemic Nitroglycerin Treatment: Interaction with Anandamide

Migraines are a frequently occurring neurological condition that affects up to 16% of the global population. The precise pathomechanism of the disease remains unknown, but from animal and human observations, it appears that calcium/calmodulin-dependent protein kinase II alpha (CamKIIα), pituitary ad...

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Main Authors: Gábor Nagy-Grócz, Eleonóra Spekker, Tamás Körtési, Klaudia Flóra Laborc, Zsuzsanna Bohár, Annamária Fejes-Szabó, László Vécsei, Árpád Párdutz
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Language:English
Published: MDPI AG 2025-01-01
Series:Life
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Online Access:https://www.mdpi.com/2075-1729/15/2/155
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author Gábor Nagy-Grócz
Eleonóra Spekker
Tamás Körtési
Klaudia Flóra Laborc
Zsuzsanna Bohár
Annamária Fejes-Szabó
László Vécsei
Árpád Párdutz
author_facet Gábor Nagy-Grócz
Eleonóra Spekker
Tamás Körtési
Klaudia Flóra Laborc
Zsuzsanna Bohár
Annamária Fejes-Szabó
László Vécsei
Árpád Párdutz
author_sort Gábor Nagy-Grócz
collection DOAJ
description Migraines are a frequently occurring neurological condition that affects up to 16% of the global population. The precise pathomechanism of the disease remains unknown, but from animal and human observations, it appears that calcium/calmodulin-dependent protein kinase II alpha (CamKIIα), pituitary adenylate cyclase-activating polypeptide (PACAP), and vasoactive intestinal polypeptide (VIP) are involved in its pathogenesis. One of the animal models of migraines uses the systemic administration of nitroglycerin (NTG), which, as a nitric oxide (NO) donor, initiates a self-amplifying process in the trigeminal system, leading to central sensitization. Endocannabinoids, such as anandamide (AEA), are thought to play a modulatory role in trigeminal activation and sensitization phenomena. In the present experiment, we aimed to investigate the effect of NTG and AEA on CamKIIα, PACAP/VIP, and vasoactive intestinal polypeptide type 1 receptor (VPAC1) expression levels in the upper cervical spinal cord (C1-C2) of rats, where trigeminal nociceptive afferents are clustered. Four groups of animals were formed: in the first group, the rats received only the vehicle; in the second group, they were treated with an intraperitoneal injection of NTG (10 mg/kg); animals in the third and fourth groups received AEA (2 × 5 mg/kg) half an hour before and one hour after the placebo or treatment with NTG. Four hours after the placebo/NTG injection, the animals were transcardially perfused, and the cervical spinal cords were removed for Western blot. Our results show that both NTG and AEA alone can increase the expression of CamKIIα and VPAC1 in the C1-C2 segments. Interestingly, the combination of NTG and AEA had no such effect on these markers, possibly due to various negative feedback mechanisms.
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spelling doaj-art-1bde9569526048c8be7f8e9f9dc28b4f2025-08-20T02:03:25ZengMDPI AGLife2075-17292025-01-0115215510.3390/life15020155CamKIIα and VPAC1 Expressions in the Caudal Trigeminal Nucleus of Rats After Systemic Nitroglycerin Treatment: Interaction with AnandamideGábor Nagy-Grócz0Eleonóra Spekker1Tamás Körtési2Klaudia Flóra Laborc3Zsuzsanna Bohár4Annamária Fejes-Szabó5László Vécsei6Árpád Párdutz7Department of Theoretical Health Sciences and Health Management, Faculty of Health Sciences and Social Studies, University of Szeged, Temesvári Krt. 31, H-6726 Szeged, HungaryCompetence Centre for Drug Development and Clinical Trials, Centre of Excellence for Interdisciplinary Research, Development and Innovation, Korányi Fasor 6, H-6720 Szeged, HungaryDepartment of Theoretical Health Sciences and Health Management, Faculty of Health Sciences and Social Studies, University of Szeged, Temesvári Krt. 31, H-6726 Szeged, HungaryNeuropathology Brain Bank & Research CoRE, Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USAHUN-REN-SZTE Neuroscience Research Group, University of Szeged, Semmelweis u. 6, H-6725 Szeged, HungaryHUN-REN-SZTE Neuroscience Research Group, University of Szeged, Semmelweis u. 6, H-6725 Szeged, HungaryHUN-REN-SZTE Neuroscience Research Group, University of Szeged, Semmelweis u. 6, H-6725 Szeged, HungaryDepartment of Neurology, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, HungaryMigraines are a frequently occurring neurological condition that affects up to 16% of the global population. The precise pathomechanism of the disease remains unknown, but from animal and human observations, it appears that calcium/calmodulin-dependent protein kinase II alpha (CamKIIα), pituitary adenylate cyclase-activating polypeptide (PACAP), and vasoactive intestinal polypeptide (VIP) are involved in its pathogenesis. One of the animal models of migraines uses the systemic administration of nitroglycerin (NTG), which, as a nitric oxide (NO) donor, initiates a self-amplifying process in the trigeminal system, leading to central sensitization. Endocannabinoids, such as anandamide (AEA), are thought to play a modulatory role in trigeminal activation and sensitization phenomena. In the present experiment, we aimed to investigate the effect of NTG and AEA on CamKIIα, PACAP/VIP, and vasoactive intestinal polypeptide type 1 receptor (VPAC1) expression levels in the upper cervical spinal cord (C1-C2) of rats, where trigeminal nociceptive afferents are clustered. Four groups of animals were formed: in the first group, the rats received only the vehicle; in the second group, they were treated with an intraperitoneal injection of NTG (10 mg/kg); animals in the third and fourth groups received AEA (2 × 5 mg/kg) half an hour before and one hour after the placebo or treatment with NTG. Four hours after the placebo/NTG injection, the animals were transcardially perfused, and the cervical spinal cords were removed for Western blot. Our results show that both NTG and AEA alone can increase the expression of CamKIIα and VPAC1 in the C1-C2 segments. Interestingly, the combination of NTG and AEA had no such effect on these markers, possibly due to various negative feedback mechanisms.https://www.mdpi.com/2075-1729/15/2/155migrainetrigeminal systemnitroglycerinanandamideCamKIIαPACAP
spellingShingle Gábor Nagy-Grócz
Eleonóra Spekker
Tamás Körtési
Klaudia Flóra Laborc
Zsuzsanna Bohár
Annamária Fejes-Szabó
László Vécsei
Árpád Párdutz
CamKIIα and VPAC1 Expressions in the Caudal Trigeminal Nucleus of Rats After Systemic Nitroglycerin Treatment: Interaction with Anandamide
Life
migraine
trigeminal system
nitroglycerin
anandamide
CamKIIα
PACAP
title CamKIIα and VPAC1 Expressions in the Caudal Trigeminal Nucleus of Rats After Systemic Nitroglycerin Treatment: Interaction with Anandamide
title_full CamKIIα and VPAC1 Expressions in the Caudal Trigeminal Nucleus of Rats After Systemic Nitroglycerin Treatment: Interaction with Anandamide
title_fullStr CamKIIα and VPAC1 Expressions in the Caudal Trigeminal Nucleus of Rats After Systemic Nitroglycerin Treatment: Interaction with Anandamide
title_full_unstemmed CamKIIα and VPAC1 Expressions in the Caudal Trigeminal Nucleus of Rats After Systemic Nitroglycerin Treatment: Interaction with Anandamide
title_short CamKIIα and VPAC1 Expressions in the Caudal Trigeminal Nucleus of Rats After Systemic Nitroglycerin Treatment: Interaction with Anandamide
title_sort camkiiα and vpac1 expressions in the caudal trigeminal nucleus of rats after systemic nitroglycerin treatment interaction with anandamide
topic migraine
trigeminal system
nitroglycerin
anandamide
CamKIIα
PACAP
url https://www.mdpi.com/2075-1729/15/2/155
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