Neuronal complexity is attenuated in chronic migraine and restored by HDAC6 inhibition
Neuronal complexity is attenuated in chronic migraine and restored by HDAC6 inhibition
Abstract Migraine is the third most prevalent disease worldwide and current therapies provide only partial relief. Greater insight into molecular migraine mechanisms would create novel therapies. Cytoskeletal flexibility is fundamental to neuronal-plasticity and is dependent on microtubule dynamicity. Histone-deacetylase-6 (HDAC6) decreases microtubule dynamics by deacetylating its primary substrate, α-tubulin. We use validated models of chronic migraine to show that HDAC6-inhibition is an effective migraine treatment and reveal an undiscovered cytoarchitectural basis for migraine chronicity. The human migraine trigger, nitroglycerin, produced chronic migraine-associated pain and decreased neurite growth in pain-processing regions, and these were reversed by HDAC6 inhibition. Cortical spreading depression (CSD), a physiological correlate of migraine aura, also caused decreased cortical neurite growth, while administration of HDAC6-inhibitor restored neuronal complexity and decreased CSD. Our results demonstrate that disruptions in neuronal cytoarchitecture are a feature of chronic migraine, and evolving migraine therapies might include agents that restore microtubule stability and neuronal plasticity.
Pradhan Amynah A、Bertels Zachariah、Singh Harinder、Dripps Isaac、Petukhova Valentina、Petukhov Pavel A.、Baca Serapio M.、Conway Catherine、Sheets Zoie、Witkowski Wiktor、Tipton Alycia F、Siegersma Kendra、Rasenick Mark M、Shah Pal、Karumudi Bhargava
Department of Psychiatry, University of Illinois at ChicagoDepartment of Psychiatry, University of Illinois at ChicagoDepartment of Physiology and Biophysics, University of Illinois at ChicagoDepartment of Psychiatry, University of Illinois at ChicagoDepartment of Medicinal Chemistry and Pharmacognosy, University of Illinois at ChicagoDepartment of Medicinal Chemistry and Pharmacognosy, University of Illinois at ChicagoDepartment of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus||Department of Neurology, University of Colorado Anschutz Medical CampusDepartment of Psychiatry, University of Illinois at ChicagoDepartment of Psychiatry, University of Illinois at ChicagoDepartment of Psychiatry, University of Illinois at ChicagoDepartment of Psychiatry, University of Illinois at ChicagoDepartment of Psychiatry, University of Illinois at ChicagoDepartment of Psychiatry, University of Illinois at Chicago||Department of Physiology and Biophysics, University of Illinois at Chicago||Jesse Brown VAMCDepartment of Psychiatry, University of Illinois at ChicagoDepartment of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago
神经病学、精神病学基础医学分子生物学
Pradhan Amynah A,Bertels Zachariah,Singh Harinder,Dripps Isaac,Petukhova Valentina,Petukhov Pavel A.,Baca Serapio M.,Conway Catherine,Sheets Zoie,Witkowski Wiktor,Tipton Alycia F,Siegersma Kendra,Rasenick Mark M,Shah Pal,Karumudi Bhargava.Neuronal complexity is attenuated in chronic migraine and restored by HDAC6 inhibition[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2020.04.21.053272.点此复制
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