Academic Journal

Pituitary adenylate cyclase-activating polypeptide plays a key role in nitroglycerol-induced trigeminovascular activation in mice

التفاصيل البيبلوغرافية
العنوان: Pituitary adenylate cyclase-activating polypeptide plays a key role in nitroglycerol-induced trigeminovascular activation in mice
المؤلفون: Adrienn Markovics, Viktoria Kormos, Balazs Gaszner, Arvin Lashgarara, Eva Szoke, Katalin Sandor, Krisztina Szabadfi, Bernadett Tuka, Janos Tajti, Janos Szolcsanyi, Erika Pinter, Hitoshi Hashimoto, Jozsef Kun, Dora Reglodi, Zsuzsanna Helyes
المصدر: Neurobiology of Disease, Vol 45, Iss 1, Pp 633-644 (2012)
بيانات النشر: Elsevier, 2012.
سنة النشر: 2012
المجموعة: LCC:Neurosciences. Biological psychiatry. Neuropsychiatry
مصطلحات موضوعية: Light-aversive behavior, Light–dark box, Laser Doppler blood perfusion scanning, Meningeal microcirculation, c-Fos immunohistochemistry, PAC1 receptor immunohistochemistry, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
الوصف: Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors (PAC1, VPAC) are present in sensory neurons and vascular smooth muscle. PACAP infusion was found to trigger migraine-like headache in humans and we showed its central pro-nociceptive function in several mouse pain models. Nitroglycerol (NTG)-induced pathophysiological changes were investigated in this study in PACAP gene-deleted (PACAP−/−) and wildtype (PACAP+/+) mice. Chemical activation of the trigeminovascular system was induced by 10 mg/kg i.p. NTG. Light-aversive behavior was determined in a light–dark box, meningeal microcirculation by laser Doppler blood perfusion scanning and the early neuronal activation marker c-Fos with immunohistochemistry. NTG-induced photophobia both in the early (0–30 min) and late phases (90–120 min) due to direct vasodilation and trigeminal sensitization, respectively, was significantly reduced in PACAP−/− mice. Meningeal blood flow increased by 30–35% during 4 h in PACAP+/+ mice, but only a 5–10% elevation occurred from the second hour in PACAP−/− ones. The number of c-Fos expressing cells referring to neuronal activation in the trigeminal ganglia and nucleus caudalis significantly increased 4 h after NTG in PACAP+/+, but not in PACAP−/− animals. Similar PAC1 receptor immunostaining was detected in both groups, which did not change 4 h after NTG treatment. PACAP-38 (300 μg/kg, i.p.) produced photophobia similarly to NTG and 30% meningeal vasodilatation for 30 min in PACAP+/+, but not in PACAP−/− mice. It significantly increased neural activation 4 h later in the trigeminal ganglia of both groups, but in the nucleus caudalis of only the PACAP+/+ mice.We provide the first experimental results that PACAP is a pivotal mediator of trigeminovascular activation/sensitization and meningeal vasodilation related to migraine.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1095-953X
Relation: http://www.sciencedirect.com/science/article/pii/S0969996111003421; https://doaj.org/toc/1095-953X
DOI: 10.1016/j.nbd.2011.10.010
URL الوصول: https://doaj.org/article/af168d60755641929d761c3edfb1b7ff
رقم الانضمام: edsdoj.f168d60755641929d761c3edfb1b7ff
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:1095953X
DOI:10.1016/j.nbd.2011.10.010