Back to Search
Start Over
Neuronal complexity is attenuated in preclinical models of migraine and restored by HDAC6 inhibition.
- Source :
-
ELife [Elife] 2021 Apr 15; Vol. 10. Date of Electronic Publication: 2021 Apr 15. - Publication Year :
- 2021
-
Abstract
- Migraine is the sixth most prevalent disease worldwide but the mechanisms that underlie migraine chronicity are poorly understood. Cytoskeletal flexibility is fundamental to neuronal-plasticity and is dependent on dynamic microtubules. Histone-deacetylase-6 (HDAC6) decreases microtubule dynamics by deacetylating its primary substrate, α-tubulin. We use validated mouse models of migraine to show that HDAC6-inhibition is a promising 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 headache-processing regions, which were reversed by HDAC6 inhibition. Cortical spreading depression (CSD), a physiological correlate of migraine aura, also decreased cortical neurite growth, while HDAC6-inhibitor restored neuronal complexity and decreased CSD. Importantly, a calcitonin gene-related peptide receptor antagonist also restored blunted neuronal complexity induced by nitroglycerin. Our results demonstrate that disruptions in neuronal cytoarchitecture are a feature of chronic migraine, and effective migraine therapies might include agents that restore microtubule/neuronal plasticity.<br />Competing Interests: ZB, HS, ID, KS, AT, WW, ZS, PS, CC, EM, MA, VP, BK, PP, SB, MR, AP No competing interests declared<br /> (© 2021, Bertels et al.)
- Subjects :
- Acetylation
Animals
Behavior, Animal drug effects
Brain enzymology
Brain physiopathology
Calcitonin Gene-Related Peptide Receptor Antagonists pharmacology
Cortical Spreading Depression drug effects
Disease Models, Animal
Female
Histone Deacetylase 6 metabolism
Male
Mice, Inbred C57BL
Microtubules enzymology
Microtubules pathology
Migraine Disorders chemically induced
Migraine Disorders enzymology
Migraine Disorders physiopathology
Neuronal Outgrowth drug effects
Neurons enzymology
Neurons pathology
Nitroglycerin
Pain Perception drug effects
Pain Threshold drug effects
Protein Processing, Post-Translational
Receptors, Calcitonin Gene-Related Peptide drug effects
Receptors, Calcitonin Gene-Related Peptide metabolism
Mice
Brain drug effects
Histone Deacetylase 6 antagonists & inhibitors
Histone Deacetylase Inhibitors pharmacology
Microtubules drug effects
Migraine Disorders drug therapy
Neuronal Plasticity drug effects
Neurons drug effects
Tubulin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 10
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 33856345
- Full Text :
- https://doi.org/10.7554/eLife.63076