PMID- 34370177 OWN - NLM STAT- MEDLINE DCOM- 20220324 LR - 20220324 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 58 IP - 11 DP - 2021 Nov TI - Involvement of TRPM2 in the Neurobiology of Experimental Migraine: Focus on Oxidative Stress and Apoptosis. PG - 5581-5601 LID - 10.1007/s12035-021-02503-w [doi] AB - Excessive Ca(2+) 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 Ca(2+) levels, and cytokine generations (TNF-alpha, IL-1beta, 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. CI - (c) 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Yazgan, Yener AU - Yazgan Y AD - Department of Neuroscience, Health Science Institute, Suleyman Demirel University, Isparta, Turkey. FAU - Naziroglu, Mustafa AU - Naziroglu M AD - Department of Neuroscience, Health Science Institute, Suleyman Demirel University, Isparta, Turkey. mustafanaziroglu@sdu.edu.tr. AD - Neuroscience Research Center, Suleyman Demirel University, Isparta, Turkey. mustafanaziroglu@sdu.edu.tr. AD - Drug Discovery Unit, BSN Health, Analyses, Innovation, Consultancy, Organization, Agriculture and Industry Ltd, Isparta, Turkey. mustafanaziroglu@sdu.edu.tr. AD - Department of Biophysics, Faculty of Medicine, Suleyman Demirel University, TR-32260, Isparta, Turkey. mustafanaziroglu@sdu.edu.tr. LA - eng GR - TDK-2020-7448/suleyman demirel universitesi/ PT - Journal Article DEP - 20210809 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (Boron Compounds) RN - 0 (Cinnamates) RN - 0 (Cytokines) RN - 0 (N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride) RN - 0 (Phenanthrenes) RN - 0 (Poly(ADP-ribose) Polymerase Inhibitors) RN - 0 (TRPM Cation Channels) RN - 0 (TRPM2 protein, mouse) RN - 0 (ortho-Aminobenzoates) RN - 110683-10-8 (4-amylcinnamoylanthranilic acid) RN - 20762-30-5 (Adenosine Diphosphate Ribose) RN - E4ES684O93 (2-aminoethoxydiphenyl borate) RN - EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1) RN - EC 3.4.22.- (Caspases) RN - G59M7S0WS3 (Nitroglycerin) RN - GAN16C9B8O (Glutathione) SB - IM MH - Adenosine Diphosphate Ribose/metabolism MH - Animals MH - Apoptosis MH - Boron Compounds/pharmacology MH - Calcium Signaling MH - Caspases/metabolism MH - Cinnamates/pharmacology MH - Cytokines/biosynthesis/genetics MH - Enzyme Activation MH - Glutathione/metabolism MH - Hyperalgesia/etiology/physiopathology MH - Lipid Peroxidation MH - Membrane Potential, Mitochondrial/physiology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Migraine Disorders/chemically induced/*metabolism/physiopathology MH - Neuroinflammatory Diseases MH - Neurons/pathology MH - Nitroglycerin/toxicity MH - Oxidative Stress MH - Phenanthrenes/pharmacology MH - Poly (ADP-Ribose) Polymerase-1/antagonists & inhibitors/metabolism MH - Poly(ADP-ribose) Polymerase Inhibitors/pharmacology MH - TRPM Cation Channels/antagonists & inhibitors/deficiency/*physiology MH - Trigeminal Ganglion/drug effects/*metabolism MH - ortho-Aminobenzoates/pharmacology OTO - NOTNLM OT - Apoptosis OT - Migraine OT - Oxidative stress OT - PARP1 OT - TRPM2 channel OT - Trigeminal ganglia EDAT- 2021/08/10 06:00 MHDA- 2022/03/25 06:00 CRDT- 2021/08/09 12:31 PHST- 2021/06/17 00:00 [received] PHST- 2021/07/20 00:00 [accepted] PHST- 2021/08/10 06:00 [pubmed] PHST- 2022/03/25 06:00 [medline] PHST- 2021/08/09 12:31 [entrez] AID - 10.1007/s12035-021-02503-w [pii] AID - 10.1007/s12035-021-02503-w [doi] PST - ppublish SO - Mol Neurobiol. 2021 Nov;58(11):5581-5601. doi: 10.1007/s12035-021-02503-w. Epub 2021 Aug 9.