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Stress hormone corticosterone enhances susceptibility to cortical spreading depression in familial hemiplegic migraine type 1 mutant mice.
Exp Neurol 2015; 263:214-20EN

Abstract

Stress is a putative migraine trigger, but the pathogenic mechanisms involved are unknown. Stress and stress hormones increase neuronal excitability by enhancing glutamatergic neurotransmission, but inhibitory effects have also been reported. We hypothesise that an acute rise in stress hormones, such as corticosteroids which are released after stress, increase neuronal excitability and thereby may increase susceptibility to cortical spreading depression (CSD), the mechanism underlying the migraine aura. Here we investigated effects of acute restraint stress and of the stress hormone corticosterone on CSD susceptibility as surrogate migraine marker, in a transgenic mouse model of familial hemiplegic migraine type 1 (FHM1), which displays increased glutamatergic cortical neurotransmission and increased propensity for CSD. We found that 20-min and 3-h restraint stress did not influence CSD susceptibility in mutant or wild-type mice, despite elevated levels of plasma corticosterone. By contrast, subcutaneous administration of 20mg/kg corticosterone increased CSD frequency exclusively in mutant mice, while corticosterone plasma levels were similarly elevated in mutants and wild types. The effect of corticosterone on CSD frequency was normalised by pre-administration of the glucocorticoid receptor (GR) antagonist mifepristone. These findings suggest that corticosteroid-induced GR activation can enhance susceptibility to CSD in genetically susceptible individuals, and may predispose to attacks of migraine. Although corticosterone levels rise also during acute stress, the latter likely triggers a spatiotemporally more complex biological response with multiple positive and negative modulators which may not be adequately modeled by exogenous administration of corticosterone alone.

Authors+Show Affiliations

Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.Stroke Service and Neuroscience Intensive Care Unit, Department of Neurology, MA General Hospital, Harvard Medical School, Charlestown, USA.Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.Neurovascular Research Laboratory, Department of Radiology, MA General Hospital, Harvard Medical School, Charlestown, USA; Stroke Service and Neuroscience Intensive Care Unit, Department of Neurology, MA General Hospital, Harvard Medical School, Charlestown, USA.Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Rudolf Magnus Institute of Neuroscience, Utrecht, The Netherlands.Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: E.A.Tolner@lumc.nl.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25447936

Citation

Shyti, Reinald, et al. "Stress Hormone Corticosterone Enhances Susceptibility to Cortical Spreading Depression in Familial Hemiplegic Migraine Type 1 Mutant Mice." Experimental Neurology, vol. 263, 2015, pp. 214-20.
Shyti R, Eikermann-Haerter K, van Heiningen SH, et al. Stress hormone corticosterone enhances susceptibility to cortical spreading depression in familial hemiplegic migraine type 1 mutant mice. Exp Neurol. 2015;263:214-20.
Shyti, R., Eikermann-Haerter, K., van Heiningen, S. H., Meijer, O. C., Ayata, C., Joëls, M., ... Tolner, E. A. (2015). Stress hormone corticosterone enhances susceptibility to cortical spreading depression in familial hemiplegic migraine type 1 mutant mice. Experimental Neurology, 263, pp. 214-20. doi:10.1016/j.expneurol.2014.10.015.
Shyti R, et al. Stress Hormone Corticosterone Enhances Susceptibility to Cortical Spreading Depression in Familial Hemiplegic Migraine Type 1 Mutant Mice. Exp Neurol. 2015;263:214-20. PubMed PMID: 25447936.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stress hormone corticosterone enhances susceptibility to cortical spreading depression in familial hemiplegic migraine type 1 mutant mice. AU - Shyti,Reinald, AU - Eikermann-Haerter,Katharina, AU - van Heiningen,Sandra H, AU - Meijer,Onno C, AU - Ayata,Cenk, AU - Joëls,Marian, AU - Ferrari,Michel D, AU - van den Maagdenberg,Arn M J M, AU - Tolner,Else A, Y1 - 2014/10/29/ PY - 2014/05/05/received PY - 2014/09/25/revised PY - 2014/10/22/accepted PY - 2014/12/3/entrez PY - 2014/12/3/pubmed PY - 2015/2/11/medline KW - Ca(V)2.1 calcium channels KW - Cortical spreading depression KW - Corticosterone KW - Familial hemiplegic migraine KW - Glutamate KW - Migraine KW - Neuronal hyperexcitability KW - Stress SP - 214 EP - 20 JF - Experimental neurology JO - Exp. Neurol. VL - 263 N2 - Stress is a putative migraine trigger, but the pathogenic mechanisms involved are unknown. Stress and stress hormones increase neuronal excitability by enhancing glutamatergic neurotransmission, but inhibitory effects have also been reported. We hypothesise that an acute rise in stress hormones, such as corticosteroids which are released after stress, increase neuronal excitability and thereby may increase susceptibility to cortical spreading depression (CSD), the mechanism underlying the migraine aura. Here we investigated effects of acute restraint stress and of the stress hormone corticosterone on CSD susceptibility as surrogate migraine marker, in a transgenic mouse model of familial hemiplegic migraine type 1 (FHM1), which displays increased glutamatergic cortical neurotransmission and increased propensity for CSD. We found that 20-min and 3-h restraint stress did not influence CSD susceptibility in mutant or wild-type mice, despite elevated levels of plasma corticosterone. By contrast, subcutaneous administration of 20mg/kg corticosterone increased CSD frequency exclusively in mutant mice, while corticosterone plasma levels were similarly elevated in mutants and wild types. The effect of corticosterone on CSD frequency was normalised by pre-administration of the glucocorticoid receptor (GR) antagonist mifepristone. These findings suggest that corticosteroid-induced GR activation can enhance susceptibility to CSD in genetically susceptible individuals, and may predispose to attacks of migraine. Although corticosterone levels rise also during acute stress, the latter likely triggers a spatiotemporally more complex biological response with multiple positive and negative modulators which may not be adequately modeled by exogenous administration of corticosterone alone. SN - 1090-2430 UR - https://www.unboundmedicine.com/medline/citation/25447936/Stress_hormone_corticosterone_enhances_susceptibility_to_cortical_spreading_depression_in_familial_hemiplegic_migraine_type_1_mutant_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(14)00351-3 DB - PRIME DP - Unbound Medicine ER -