Neuronal complexity is attenuated in chronic migraine and restored by HDAC6 inhibition [article]

Zachariah Bertels, Harinder Grewal, Isaac Dripps, Kendra Siegersma, Alycia Laboy, Wiktor Witkowski, Zoie Sheets, Pal Shah, Catherine Conway, Valentina Petukhova, Bhargava Karumudi, Pavel A Petukhov (+3 others)
2020 bioRxiv   pre-print
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
more » ... aine 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.
doi:10.1101/2020.04.21.053272 fatcat:2p77xyu27je4pkdaddz72n3gpm