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Involvement of TRPM2 in the Neurobiology of Experimental Migraine: Focus on Oxidative Stress and Apoptosis       
Yazarlar
Dr. Öğr. Üyesi Yener YAZĞAN
Kastamonu Üniversitesi, Türkiye
Mustafa Nazıroğlu
Süleyman Demirel Üniversitesi, Türkiye
Özet
Excessive Ca2+ influx and mitochondrial oxidative stress (OS) of trigeminal ganglia (TG) have essential roles in the etiology of migraine headache and aura. The stimulation of TRPM2 channel via the generation of OS and ADP-ribose (ADPR) induces pain, inflammatory, and oxidative neurotoxicity, although its inhibition reduces the intensity of pain and neurotoxicity in several neurons. However, the cellular and molecular effects of TRPM2 in the TG of migraine model (glyceryl trinitrate, GTN) on the induction of pain, OS, apoptosis, and inflammation remain elusive. GTN-mediated increases of pain intensity, apoptosis, death, cytosolic reactive oxygen species (ROS), mitochondrial ROS, caspase -3, caspase -9, cytosolic Ca2+ levels, and cytokine generations (TNF-α, IL-1β, and IL-6) in the TG of TRPM2 wild-type mouse were further increased by the TRPM2 activation, although they were modulated by the treatments of GSH, PARP-1 inhibitors (PJ34 and DPQ), and TRPM2 blockers (ACA and 2APB). However, the effects of GTN were not observed in the TG of TRPM2 knockout mice. The current data indicate that the maintaining activation of TRPM2 is not only important for the quenching OS, inflammation, and neurotoxicity in the TG neurons of mice with experimental migraine but also equally critical to the modulation of GTN-induced pain.
Anahtar Kelimeler
Apoptosis,Migraine,Oxidative stress,PARP1,Trigeminal ganglia,TRPM2 channel
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı Molecular Neurobiology
Dergi ISSN 0893-7648
Dergi Tarandığı Indeksler SCI-Expanded
Dergi Grubu Q2
Makale Dili İngilizce
Basım Tarihi 01-2021
Cilt No 58
Doi Numarası 10.1007/s12035-021-02503-w
Makale Linki http://dx.doi.org/10.1007/s12035-021-02503-w