Mitochondrial metabolism related markers GDF-15, FGF-21, and HIF-1α are elevated in pediatric migraine attacks.


Journal

Headache
ISSN: 1526-4610
Titre abrégé: Headache
Pays: United States
ID NLM: 2985091R

Informations de publication

Date de publication:
09 2023
Historique:
revised: 14 07 2023
received: 20 04 2023
accepted: 24 07 2023
medline: 20 9 2023
pubmed: 19 8 2023
entrez: 19 8 2023
Statut: ppublish

Résumé

The purpose of this study was to investigate the serum levels of mitochondrial metabolism/reactive oxygen species (ROS)-related peptides (hypoxia inducible factor-1α [HIF-1α], fibroblast growth factor-21 [FGF-21], growth differentiation factor-15 [GDF-15]) and key migraine-related neuropeptides (calcitonin gene-related peptide [CGRP], pituitary adenylate cyclase-activating peptide-38 [PACAP-38], substance P [SP], and vasoactive intestinal peptide [VIP]) during migraine attacks and to evaluate their diagnostic value in pediatric migraine. There is increasing evidence for the important role of impairment in oxidative mitochondrial metabolism in the pathophysiology of migraine. Potential biomarkers that may reflect the relationship between migraine and mitochondrial dysfunction are unclear. A total of 68 female pediatric migraine patients without aura and 20 female healthy controls aged 8-18 years, admitted to the hospital, were enrolled in this cross-sectional study. Serum concentrations of these molecules were determined by enzyme-linked immunosorbent assays, and clinical features and their possible diagnostic value were analyzed. Serum levels of HIF-1α (252.4 ± 51.9 [mean ± standard deviation]) pg/mL), GDF-15 (233.7 ± 24.7 pg/mL), FGF-21 (96.1 ± 13.1 pg/mL), CGRP (44.5 ± 11.3), and PACAP-38 (504.7 ± 128.9) were significantly higher in migraine patients compared to healthy controls (199.8 ± 26.8, 192.8 ± 20.7, 79.3 ± 4.1, 34.1 ± 3.5 and 361.2 ± 86.3 pg/mL, respectively). The serum levels of these peptides were also higher in patients with chronic migraine than in patients with episodic migraine, and higher in the ictal period than in the interictal period. A positive correlation was found between attack frequency and both HIF-1α and FGF-21 levels in migraine patients. Serum levels of VIP and SP were not different between the migraine patients and healthy controls. Migraine attacks are accompanied by elevated HIF-1α, FGF-21, GDF-15, CGRP, and PACAP-38 in medication-naive pediatric patients with migraine. Elevated circulating mitochondrial metabolism/ROS-related peptides suggest a mitochondrial stress in pediatric migraine attacks and may have potential diagnostic value in monitoring disease progression and treatment response in children. Novel approaches intervening with mitochondrial metabolism need to be investigated.

Sections du résumé

OBJECTIVE
The purpose of this study was to investigate the serum levels of mitochondrial metabolism/reactive oxygen species (ROS)-related peptides (hypoxia inducible factor-1α [HIF-1α], fibroblast growth factor-21 [FGF-21], growth differentiation factor-15 [GDF-15]) and key migraine-related neuropeptides (calcitonin gene-related peptide [CGRP], pituitary adenylate cyclase-activating peptide-38 [PACAP-38], substance P [SP], and vasoactive intestinal peptide [VIP]) during migraine attacks and to evaluate their diagnostic value in pediatric migraine.
BACKGROUND
There is increasing evidence for the important role of impairment in oxidative mitochondrial metabolism in the pathophysiology of migraine. Potential biomarkers that may reflect the relationship between migraine and mitochondrial dysfunction are unclear.
METHODS
A total of 68 female pediatric migraine patients without aura and 20 female healthy controls aged 8-18 years, admitted to the hospital, were enrolled in this cross-sectional study. Serum concentrations of these molecules were determined by enzyme-linked immunosorbent assays, and clinical features and their possible diagnostic value were analyzed.
RESULTS
Serum levels of HIF-1α (252.4 ± 51.9 [mean ± standard deviation]) pg/mL), GDF-15 (233.7 ± 24.7 pg/mL), FGF-21 (96.1 ± 13.1 pg/mL), CGRP (44.5 ± 11.3), and PACAP-38 (504.7 ± 128.9) were significantly higher in migraine patients compared to healthy controls (199.8 ± 26.8, 192.8 ± 20.7, 79.3 ± 4.1, 34.1 ± 3.5 and 361.2 ± 86.3 pg/mL, respectively). The serum levels of these peptides were also higher in patients with chronic migraine than in patients with episodic migraine, and higher in the ictal period than in the interictal period. A positive correlation was found between attack frequency and both HIF-1α and FGF-21 levels in migraine patients. Serum levels of VIP and SP were not different between the migraine patients and healthy controls.
CONCLUSION
Migraine attacks are accompanied by elevated HIF-1α, FGF-21, GDF-15, CGRP, and PACAP-38 in medication-naive pediatric patients with migraine. Elevated circulating mitochondrial metabolism/ROS-related peptides suggest a mitochondrial stress in pediatric migraine attacks and may have potential diagnostic value in monitoring disease progression and treatment response in children. Novel approaches intervening with mitochondrial metabolism need to be investigated.

Identifiants

pubmed: 37596867
doi: 10.1111/head.14618
doi:

Substances chimiques

fibroblast growth factor 21 0
Growth Differentiation Factor 15 0
Calcitonin Gene-Related Peptide JHB2QIZ69Z
Pituitary Adenylate Cyclase-Activating Polypeptide 0
Reactive Oxygen Species 0
Fibroblast Growth Factors 62031-54-3

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1076-1086

Subventions

Organisme : Gazi University
ID : TGA-2022-7857
Organisme : Turkish Academy of Sciences (TUBA)

Informations de copyright

© 2023 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.

Références

Onofri A, Pensato U, Rosignoli C, et al. Primary headache epidemiology in children and adolescents: a systematic review and meta-analysis. J Headache Pain. 2023;24(1):8.
Wöber-Bingöl C. Epidemiology of migraine and headache in children and adolescents. Curr Pain Headache Rep. 2013;17(6):341.
Gross EC, Putananickal N, Orsini AL, et al. Mitochondrial function and oxidative stress markers in higher-frequency episodic migraine. Sci Rep. 2021;11(1):4543.
Bernecker C, Ragginer C, Fauler G, et al. Oxidative stress is associated with migraine and migraine-related metabolic risk in females. Eur J Neurol. 2011;18(10):1233-1239.
Tripathi GM, Kalita J, Misra UK. A study of oxidative stress in migraine with special reference to prophylactic therapy. Int J Neurosci. 2018;128(4):318-324.
Aytaç B, Coşkun Ö, Alioğlu B, et al. Decreased antioxidant status in migraine patients with brain white matter hyperintensities. Neurol Sci. 2014;35(12):1925-1929.
Sparaco M, Feleppa M, Lipton RB, Rapoport AM, Bigal ME. Mitochondrial dysfunction and migraine: evidence and hypotheses. Cephalalgia. 2006;26(4):361-372.
Uncini A, Lodi R, Di Muzio A, et al. Abnormal brain and muscle energy metabolism shown by 31P-MRS in familial hemiplegic migraine. J Neurol Sci. 1995;129(2):214-222.
Kausar S, Wang F, Cui H. The role of mitochondria in reactive oxygen species generation and its implications for neurodegenerative diseases. Cell. 2018;7(12):274.
Bohra SK, Achar RR, Chidambaram SB, et al. Current perspectives on mitochondrial dysfunction in migraine. Eur J Neurosci. 2022;56(1):3738-3754.
Jiang L, Ma D, Grubb BD, Wang M. ROS/TRPA1/CGRP signaling mediates cortical spreading depression. J Headache Pain. 2019;20(1):25.
Reyngoudt H, Paemeleire K, Descamps B, De Deene Y, Achten E. 31P-MRS demonstrates a reduction in high-energy phosphates in the occipital lobe of migraine without aura patients. Cephalalgia. 2011;31(12):1243-1253.
López-Armada MJ, Fernández-Rodríguez JA, Blanco FJ. Mitochondrial dysfunction and oxidative stress in rheumatoid arthritis. Antioxidants (Basel). 2022;11(6):1151.
Kim KH, Lee MS. GDF15 as a central mediator for integrated stress response and a promising therapeutic molecule for metabolic disorders and NASH. Biochim Biophys Acta Gen Subj. 2021;1865(3):129834.
Cardoso A, Fernandes A, Aguilar-Pimentel J, et al. Towards frailty biomarkers: candidates from genes and pathways regulated in aging and age-related diseases. Ageing Res Rev. 2018;47:214-277.
Davis R, Liang C, Sue C. A comparison of current serum biomarkers as diagnostic indicators of mitochondrial diseases. Neurology. 2016;86:2010-2015.
Eltzschig HK, Carmeliet P. Hypoxia and inflammation. N Engl J Med. 2011;364(7):656-665.
Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38(1):1-211.
Hanci F, Kilinc YB, Kilinc E, Turay S, Dilek M, Kabakus N. Plasma levels of vasoactive neuropeptides in pediatric patients with migraine during attack and attack-free periods. Cephalalgia. 2021;41(2):166-175.
He J, Zhou M, Zhao F, et al. FGF-21 and GDF-15 are increased in migraine and associated with the severity of migraine-related disability. J Headache Pain. 2023;24(1):28.
Citak A, Kilinc E, Torun IE, Ankarali S, Dagistan Y, Yoldas H. The effects of certain TRP channels and voltage-gated KCNQ/Kv7 channel opener retigabine on calcitonin gene-related peptide release in the trigeminovascular system. Cephalalgia. 2022;42(13):1375-1386.
Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S. Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev. 2017;97(2):553-622.
Pérez-Pereda S, Toriello-Suárez M, Ocejo-Vinyals G, et al. Serum CGRP, VIP, and PACAP usefulness in migraine: a case-control study in chronic migraine patients in real clinical practice. Mol Biol Rep. 2020;47(9):7125-7138.
Waschek JA, Baca SM, Akerman S. PACAP and migraine headache: immunomodulation of neural circuits in autonomic ganglia and brain parenchyma. J Headache Pain. 2018;19(1):23.
Silvestro M, Orologio I, Trojsi F, Tessitore A, Tedeschi G, Russo A. Effectiveness and safety of CGRP monoclonal antibodies in migraine related to mitochondrial diseases in patients with NARP and PEO syndromes. Clin Neurol Neurosurg. 2023;226:107611.
Guo S, Esserlind AL, Andersson Z, et al. Prevalence of migraine in persons with the 3243A>G mutation in mitochondrial DNA. Eur J Neurol. 2016;23(1):175-181.
Hansted AK, Bhatt DK, Olesen J, Jensen LJ, Jansen-Olesen I. Effect of TRPA1 activator allyl isothiocyanate (AITC) on rat dural and pial arteries. Pharmacol Rep. 2019;71(4):565-572.
Aubdool AA, Kodji X, Abdul-Kader N, et al. TRPA1 activation leads to neurogenic vasodilatation: involvement of reactive oxygen nitrogen species in addition to CGRP and NO. Br J Pharmacol. 2016;173(15):2419-2433.
Burow P, Haselier M, Naegel S, Scholle LM, Gaul C, Kraya T. The mitochondrial biomarkers FGF-21 and GDF-15 in patients with episodic and chronic migraine. Cell. 2021;10(9):2471.
Vetvik KG, MacGregor EA. Sex differences in the epidemiology, clinical features, and pathophysiology of migraine. Lancet Neurol. 2017;16(1):76-87.
Bolay H, Ozge A, Saginc P, et al. Gender influences headache characteristics with increasing age in migraine patients. Cephalalgia. 2015;35(9):792-800.
Pavlović JM, Allshouse AA, Santoro NF, et al. Sex hormones in women with and without migraine: evidence of migraine-specific hormone profiles. Neurology. 2016;87(1):49-56.
Labastida-Ramírez A, Rubio-Beltrán E, Villalón CM, MaassenVanDenBrink A. Gender aspects of CGRP in migraine. Cephalalgia. 2019;39(3):435-444.
Cetinkaya A, Kilinc E, Camsari C, Ogun MN. Effects of estrogen and progesterone on the neurogenic inflammatory neuropeptides: implications for gender differences in migraine. Exp Brain Res. 2020;238(11):2625-2639.
Liu J, Wang G, Dan Y, Liu X. CGRP and PACAP-38 play an important role in diagnosing pediatric migraine. J Headache Pain. 2022;23(1):68.
Wiggers A, Ashina H, Hadjikhani N, et al. Brain barriers and their potential role in migraine pathophysiology. J Headache Pain. 2022;23(1):16.
Johnson KW, Morin SM, Wroblewski VJ, Johnson MP. Peripheral and central nervous system distribution of the CGRP neutralizing antibody [125I] galcanezumab in male rats. Cephalalgia. 2019;39(10):1241-1248.
Dogrukol-Ak D, Tore F, Tuncel N. Passage of VIP/PACAP/secretin family across the blood-brain barrier: therapeutic effects. Curr Pharm Des. 2004;10(12):1325-1340.
Chappa AK, Audus KL, Lunte SM. Characteristics of substance P transport across the blood-brain barrier. Pharm Res. 2006;23(6):1201-1208.
Breit SN, Brown DA, Tsai VW. The GDF15-GFRAL pathway in health and metabolic disease: friend or foe? Annu Rev Physiol. 2021;83:127-151.
Hsuchou H, Pan W, Kastin AJ. The fasting polypeptide FGF21 can enter brain from blood. Peptides. 2007;28(12):2382-2386.

Auteurs

Yasemin Baranoglu Kilinc (YB)

Department of Pediatrics, Bolu Izzet Baysal State Hospital, Bolu, Turkey.

Erkan Kilinc (E)

Department of Physiology, Bolu Abant Izzet Baysal University, Medical Faculty, Bolu, Turkey.

Aysegul Danis (A)

Department of Child Neurology, Bolu Abant Izzet Baysal University, Bolu, Turkey.

Fatma Hanci (F)

Department of Child Neurology, Bolu Abant Izzet Baysal University, Bolu, Turkey.

Sevim Turay (S)

Department of Child Neurology, Duzce University, Bolu, Turkey.

Aynur Ozge (A)

Department of Neurology, Mersin University, Medical Faculty, Mersin, Turkey.

Hayrunnisa Bolay (H)

Department of Neurology and Algology, Neuroscience and Neurotechnology Center NÖROM, Gazi University, Ankara, Turkey.

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