Differential trigeminovascular nociceptive responses in the thalamus in the familial hemiplegic migraine 1 knock-in mouse: A Fos protein study
Familial hemiplegic migraine type 1 (FHM-1) is a monogenic subtype of migraine with aura caused by missense mutations in the CACNA1A gene, which encodes the pore-forming α1 subunit of voltage-gated neuronal CaV2.1 (P/Q-type) calcium channels. Transgenic knock-in mice expressing the CACNA1A R192Q mut...
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| Format: | Article |
| Language: | English |
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Elsevier
2014-04-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996113003409 |
| _version_ | 1818733976146149376 |
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| author | JungWook Park HeuiSoo Moon Simon Akerman Philip R. Holland Michele P. Lasalandra Anna P. Andreou Michel D. Ferrari Arn M.J.M. van den Maagdenberg Peter J. Goadsby |
| author_facet | JungWook Park HeuiSoo Moon Simon Akerman Philip R. Holland Michele P. Lasalandra Anna P. Andreou Michel D. Ferrari Arn M.J.M. van den Maagdenberg Peter J. Goadsby |
| author_sort | JungWook Park |
| collection | DOAJ |
| description | Familial hemiplegic migraine type 1 (FHM-1) is a monogenic subtype of migraine with aura caused by missense mutations in the CACNA1A gene, which encodes the pore-forming α1 subunit of voltage-gated neuronal CaV2.1 (P/Q-type) calcium channels. Transgenic knock-in mice expressing the CACNA1A R192Q mutation that causes FHM-1 in patients show a greater susceptibility to cortical spreading depression, the likely underlying mechanism of typical human migraine aura. The aim of this study was to compare neuronal activation within the trigeminal pain pathways in response to nociceptive trigeminovascular stimulation in wild-type and R192Q knock-in mice. After sham surgery or electrical stimulation of the superior sagittal sinus for 2 h, or stimulation preceded by treatment with naratriptan, mice underwent intracardiac perfusion, and the brain, including the brainstem, was removed. Fos expression was measured in the trigeminocervical complex (TCC) and the lateral (ventroposteromedial, ventrolateral), medial (parafascicular, centromedian) and posterior thalamic nuclei. In the TCC of wild-type animals, the number of Fos-positive cells increased significantly following dural stimulation compared to the sham control group (P < 0.001) and decreased after naratriptan treatment (P < 0.05). In R192Q knock-in mice, there was no significant difference between the stimulated and sham (P = 0.10) or naratriptan pre-treated groups (P = 0.15). The number of Fos-positive cells in the R192Q stimulated group was significantly lower compared to the wild-type stimulated mice (P < 0.05). In the thalamus, R192Q mice tended to be more sensitive to stimulation compared to the sham control in the medial and posterior nuclei, and between the two strains of stimulated animals there was a significant difference in the centromedian (P < 0.005), and posterior nuclei (P < 0.05). The present study suggests that the FHM-1 mutation affects more rostral brain structures in this experimental paradigm, which offers a novel perspective on possible differential effects of mutations causing migraine in terms of phenotype-genotype correlations. |
| first_indexed | 2024-12-17T23:58:01Z |
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| id | doaj.art-9ef2be0927994ae1b78d1be8caedcc8b |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T23:58:01Z |
| publishDate | 2014-04-01 |
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| series | Neurobiology of Disease |
| spelling | doaj.art-9ef2be0927994ae1b78d1be8caedcc8b2022-12-21T21:28:01ZengElsevierNeurobiology of Disease1095-953X2014-04-016417Differential trigeminovascular nociceptive responses in the thalamus in the familial hemiplegic migraine 1 knock-in mouse: A Fos protein studyJungWook Park0HeuiSoo Moon1Simon Akerman2Philip R. Holland3Michele P. Lasalandra4Anna P. Andreou5Michel D. Ferrari6Arn M.J.M. van den Maagdenberg7Peter J. Goadsby8Headache Group-Department of Neurology, University of California, San Francisco, San Francisco, CA, USAHeadache Group-Department of Neurology, University of California, San Francisco, San Francisco, CA, USAHeadache Group-Department of Neurology, University of California, San Francisco, San Francisco, CA, USAHeadache Group-Department of Neurology, University of California, San Francisco, San Francisco, CA, USAHeadache Group-Department of Neurology, University of California, San Francisco, San Francisco, CA, USAHeadache Group-Department of Neurology, University of California, San Francisco, San Francisco, CA, USADepartment of Neurology, Leiden University Medical Centre, 2300 RC Leiden, The NetherlandsDepartment of Neurology, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Department of Human Genetics, Leiden University Medical Centre, 2300 RC Leiden, The NetherlandsHeadache Group-Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; NIHR-Wellcome Trust Clinical Research Facility, King's College London, UK; Corresponding author at: NIHR-Wellcome Trust Clinical Research Facility, King's College Hospital, London SE5 9PJ, UK.Familial hemiplegic migraine type 1 (FHM-1) is a monogenic subtype of migraine with aura caused by missense mutations in the CACNA1A gene, which encodes the pore-forming α1 subunit of voltage-gated neuronal CaV2.1 (P/Q-type) calcium channels. Transgenic knock-in mice expressing the CACNA1A R192Q mutation that causes FHM-1 in patients show a greater susceptibility to cortical spreading depression, the likely underlying mechanism of typical human migraine aura. The aim of this study was to compare neuronal activation within the trigeminal pain pathways in response to nociceptive trigeminovascular stimulation in wild-type and R192Q knock-in mice. After sham surgery or electrical stimulation of the superior sagittal sinus for 2 h, or stimulation preceded by treatment with naratriptan, mice underwent intracardiac perfusion, and the brain, including the brainstem, was removed. Fos expression was measured in the trigeminocervical complex (TCC) and the lateral (ventroposteromedial, ventrolateral), medial (parafascicular, centromedian) and posterior thalamic nuclei. In the TCC of wild-type animals, the number of Fos-positive cells increased significantly following dural stimulation compared to the sham control group (P < 0.001) and decreased after naratriptan treatment (P < 0.05). In R192Q knock-in mice, there was no significant difference between the stimulated and sham (P = 0.10) or naratriptan pre-treated groups (P = 0.15). The number of Fos-positive cells in the R192Q stimulated group was significantly lower compared to the wild-type stimulated mice (P < 0.05). In the thalamus, R192Q mice tended to be more sensitive to stimulation compared to the sham control in the medial and posterior nuclei, and between the two strains of stimulated animals there was a significant difference in the centromedian (P < 0.005), and posterior nuclei (P < 0.05). The present study suggests that the FHM-1 mutation affects more rostral brain structures in this experimental paradigm, which offers a novel perspective on possible differential effects of mutations causing migraine in terms of phenotype-genotype correlations.http://www.sciencedirect.com/science/article/pii/S0969996113003409MigraineAuraTrigeminovascularFamilial hemiplegic migraineCACNA1A |
| spellingShingle | JungWook Park HeuiSoo Moon Simon Akerman Philip R. Holland Michele P. Lasalandra Anna P. Andreou Michel D. Ferrari Arn M.J.M. van den Maagdenberg Peter J. Goadsby Differential trigeminovascular nociceptive responses in the thalamus in the familial hemiplegic migraine 1 knock-in mouse: A Fos protein study Neurobiology of Disease Migraine Aura Trigeminovascular Familial hemiplegic migraine CACNA1A |
| title | Differential trigeminovascular nociceptive responses in the thalamus in the familial hemiplegic migraine 1 knock-in mouse: A Fos protein study |
| title_full | Differential trigeminovascular nociceptive responses in the thalamus in the familial hemiplegic migraine 1 knock-in mouse: A Fos protein study |
| title_fullStr | Differential trigeminovascular nociceptive responses in the thalamus in the familial hemiplegic migraine 1 knock-in mouse: A Fos protein study |
| title_full_unstemmed | Differential trigeminovascular nociceptive responses in the thalamus in the familial hemiplegic migraine 1 knock-in mouse: A Fos protein study |
| title_short | Differential trigeminovascular nociceptive responses in the thalamus in the familial hemiplegic migraine 1 knock-in mouse: A Fos protein study |
| title_sort | differential trigeminovascular nociceptive responses in the thalamus in the familial hemiplegic migraine 1 knock in mouse a fos protein study |
| topic | Migraine Aura Trigeminovascular Familial hemiplegic migraine CACNA1A |
| url | http://www.sciencedirect.com/science/article/pii/S0969996113003409 |
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