The effect of P2X7 antagonism on subcortical spread of optogenetically-triggered cortical spreading depression and neuroinflammation

被引:4
作者
Uzay, Burak [1 ,4 ]
Donmez-Demir, Buket [1 ]
Ozcan, Sinem Yilmaz [1 ]
Kocak, Emine Eren [1 ,2 ]
Yemisci, Muge [1 ,3 ]
Ozdemir, Yasemin Gursoy [1 ,5 ]
Dalkara, Turgay [1 ,3 ]
Karatas, Hulya [1 ]
机构
[1] Hacettepe Univ, Inst Neurol Sci & Psychiat, TR-06100 Ankara, Turkiye
[2] Hacettepe Univ, Dept Psychiat, Ankara, Turkiye
[3] Hacettepe Univ, Dept Neurol, Ankara, Turkiye
[4] Vanderbilt Univ, Dept Pharmacol, Nashville, TN USA
[5] Koc Univ, Sch Med, Istanbul, Turkiye
关键词
Migraine; CSD; Subcortical spread; Neuroinflammation; MOUSE MODELS; RECEPTOR; MIGRAINE; ACTIVATION; MECHANISMS; PREVENTION;
D O I
10.1186/s10194-024-01807-1
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Migraine is a neurological disorder characterized by episodes of severe headache. Cortical spreading depression (CSD), the electrophysiological equivalent of migraine aura, results in opening of pannexin 1 megachannels that release ATP and triggers parenchymal neuroinflammatory signaling cascade in the cortex. Migraine symptoms suggesting subcortical dysfunction bring subcortical spread of CSD under the light. Here, we investigated the role of purinergic P2X7 receptors on the subcortical spread of CSD and its consequent neuroinflammation using a potent and selective P2X7R antagonist, JNJ-47965567. P2X7R antagonism had no effect on the CSD threshold and characteristics but increased the latency to hypothalamic voltage deflection following CSD suggesting that ATP acts as a mediator in the subcortical spread. P2X7R antagonism also prevented cortical and subcortical neuronal activation following CSD, revealed by bilateral decrease in c-fos positive neuron count, and halted CSD-induced neuroinflammation revealed by decreased neuronal HMGB1 release and decreased nuclear translocation of NF-kappa B-p65 in astrocytes. In conclusion, our data suggest that P2X7R plays a role in CSD-induced neuroinflammation, subcortical spread of CSD and CSD-induced neuronal activation hence can be a potential target.
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页数:15
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共 58 条
  • [1] International union of pharmacology LVIII: Update on the P2Y G protein-coupled nucleotide receptors: From molecular mechanisms and pathophysiology to therapy
    Abbracchio, Maria P.
    Burnstock, Geoffrey
    Boeynaems, Jean-Marie
    Barnard, Eric A.
    Boyer, Jose L.
    Kennedy, Charles
    Knight, Gillian E.
    Fumagalli, Marta
    Gachet, Christian
    Jacobson, Kenneth A.
    Weisman, Gary A.
    [J]. PHARMACOLOGICAL REVIEWS, 2006, 58 (03) : 281 - 341
  • [2] Imaging of neuroinflammation in migraine with aura A [11C] PBR28 PET/MRI study
    Albrecht, Daniel S.
    Mainero, Caterina
    Ichijo, Eri
    Ward, Noreen
    Granziera, Cristina
    Zurcher, Nicole R.
    Akeju, Oluwaseun
    Bonnier, Guillaume
    Price, Julie
    Hooker, Jacob M.
    Napadow, Vitaly
    Loggia, Marco L.
    Hadjikhani, Nouchine
    [J]. NEUROLOGY, 2019, 92 (17) : E2038 - E2050
  • [3] Increased striatal proenkephalin mRNA subsequent to production of spreading depression in rat cerebral cortex: activation of corticostriatal pathways?
    Arabia, AM
    Shen, PJ
    Gundlach, AL
    [J]. MOLECULAR BRAIN RESEARCH, 1998, 61 (1-2): : 195 - 202
  • [4] Pharmacological characterization of a novel centrally permeable P2X7 receptor antagonist: JNJ-47965567
    Bhattacharya, Anindya
    Wang, Qi
    Ao, Hong
    Shoblock, James R.
    Lord, Brian
    Aluisio, Leah
    Fraser, Ian
    Nepomuceno, Diane
    Neff, Robert A.
    Welty, Natalie
    Lovenberg, Timothy W.
    Bonaventure, Pascal
    Wickenden, Alan D.
    Letavic, Michael A.
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 2013, 170 (03) : 624 - 640
  • [5] NMDA and P2X7 Receptors Require Pannexin 1 Activation to Initiate and Maintain Nociceptive Signaling in the Spinal Cord of Neuropathic Rats
    Bravo, David
    Zepeda-Morales, Katherine
    Maturana, Carola J.
    Retamal, Jeffri S.
    Hernandez, Alejandro
    Pelissier, Teresa
    Barra, Rafael
    Saez-Briones, Patricio
    Burgos, Hector
    Constandil, Luis
    [J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2022, 23 (12)
  • [6] In vivo imaging reveals that pregabalin inhibits cortical spreading depression and propagation to subcortical brain structures
    Cain, Stuart M.
    Bohnet, Barry
    LeDue, Jeffrey
    Yung, Andrew C.
    Garcia, Esperanza
    Tyson, John R.
    Alles, Sascha R. A.
    Han, Huili
    van den Maagdenberg, Arn M. J. M.
    Kozlowski, Piotr
    MacVicar, Brian A.
    Snutch, Terrance P.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2017, 114 (09) : 2401 - 2406
  • [7] Up-regulation of P2X2, P2X4 receptor and ischemic cell death:: Prevention by P2 antagonists
    Cavaliere, F
    Florenzano, F
    Amadio, S
    Fusco, FR
    Viscomi, MT
    D'Ambrosi, N
    Vacca, F
    Sancesario, G
    Bernardi, G
    Molinari, M
    Volontè, C
    [J]. NEUROSCIENCE, 2003, 120 (01) : 85 - 98
  • [8] Cortical spreading depression and migraine
    Charles, Andrew C.
    Baca, Serapio M.
    [J]. NATURE REVIEWS NEUROLOGY, 2013, 9 (11) : 637 - 644
  • [9] Inhibition of the P2X7-PANX1 complex suppresses spreading depolarization and neuroinflammation
    Chen, Shih-Pin
    Qin, Tao
    Seidel, Jessica L.
    Zheng, Yi
    Eikermann, Matthias
    Ferrari, Michel D.
    van den Maagdenberg, Arn M. J. M.
    Moskowitz, Michael A.
    Ayata, Cenk
    Eikermann-Haerter, Katharina
    [J]. BRAIN, 2017, 140 : 1643 - 1656
  • [10] Determinants of Optogenetic Cortical Spreading Depolarizations
    Chung, David Y.
    Sadeghian, Homa
    Qin, Tao
    Lule, Sevda
    Lee, Hang
    Karakaya, Fahri
    Goins, Stacy
    Oka, Fumiaki
    Yaseen, Mohammad A.
    Houben, Thijs
    Tolner, Else A.
    van den Maagdenberg, Arn M. J. M.
    Whalen, Michael J.
    Sakadzic, Sava
    Ayata, Cenk
    [J]. CEREBRAL CORTEX, 2019, 29 (03) : 1150 - 1161