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The effect of P2X7 antagonism on subcortical spread of optogenetically-triggered cortical spreading depression and neuroinflammation.
Uzay, Burak; Donmez-Demir, Buket; Ozcan, Sinem Yilmaz; Kocak, Emine Eren; Yemisci, Muge; Ozdemir, Yasemin Gursoy; Dalkara, Turgay; Karatas, Hulya.
Afiliação
  • Uzay B; Institute of Neurological Sciences and Psychiatry, Hacettepe University, Sihhiye, Ankara, 06100, Türkiye.
  • Donmez-Demir B; Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
  • Ozcan SY; Institute of Neurological Sciences and Psychiatry, Hacettepe University, Sihhiye, Ankara, 06100, Türkiye.
  • Kocak EE; Institute of Neurological Sciences and Psychiatry, Hacettepe University, Sihhiye, Ankara, 06100, Türkiye.
  • Yemisci M; Institute of Neurological Sciences and Psychiatry, Hacettepe University, Sihhiye, Ankara, 06100, Türkiye.
  • Ozdemir YG; Department of Psychiatry, Hacettepe University, Ankara, Türkiye.
  • Dalkara T; Institute of Neurological Sciences and Psychiatry, Hacettepe University, Sihhiye, Ankara, 06100, Türkiye.
  • Karatas H; Department of Neurology, Hacettepe University, Ankara, Türkiye.
J Headache Pain ; 25(1): 120, 2024 Jul 24.
Article em En | MEDLINE | ID: mdl-39044141
ABSTRACT
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Depressão Alastrante da Atividade Elétrica Cortical / Receptores Purinérgicos P2X7 / Antagonistas do Receptor Purinérgico P2X / Doenças Neuroinflamatórias Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Depressão Alastrante da Atividade Elétrica Cortical / Receptores Purinérgicos P2X7 / Antagonistas do Receptor Purinérgico P2X / Doenças Neuroinflamatórias Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article