Mitochondrial Abnormalities in Migraine. Preliminary Findings.

Montagna, Pasquale; Sacquegna, T.; Martinelli, Paolo; Cortelli, Pietro; Bresolin, Nereo; Moggio, Maurizio; Baldrati, A.; Riva, R.; Lugaresi, E

doi:10.1111/j.1526-4610.1988.hed2807477.x

Cited by 67 publications

(63 citation statements)

References 15 publications

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“…Our more recent data has demonstrated the same strong maternal inheritance bias in CVS cases without coexisting neuromuscular disease [Boles et al, submitted for publication to Am J Med Genet]. Other data supporting a mtDNA component in the pathogenesis of migraine headache and CVS include lactic acidosis in both conditions [Montagna et al, 1988;Okada et al, 1998;Boles et al, 2003a], energy depleted urine organic acid metabolite profiles in CVS [Boles and Williams, 1999;Boles et al, 2003a]; decreased oxidative phosphorylation activities in both conditions [Montagna et al, 1988;Sangiorgi et al, 1994;Boles et al, 2003a], and reduced in vivo brain phosphocreatine to inorganic phosphate ratio by 31 P magnetic resonance spectroscopy in migraine headache [reviewed in Montagna et al, 1994].…”

Section: Introductionmentioning

confidence: 78%

Mitochondrial DNA control region sequence variation in migraine headache and cyclic vomiting syndrome

Wang

Ito

Adams

et al. 2004

American J of Med Genetics Pt A

106

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Migraine headache is a very common condition affecting about 10% of the population that results in substantial morbidity and economic loss. The two most common variants are migraine with (MA) and without (MO) aura. Often considered to be a migraine-like variant, cyclic vomiting syndrome (CVS) is a predominately childhood condition characterized by severe, discrete episodes of nausea, vomiting, and lethargy. Disease-associated mitochondrial DNA (mtDNA) sequence variants are suggested in common migraine and CVS based upon a strong bias towards the maternal inheritance of disease, and several other factors. Temporal temperature gradient gel electrophoresis (TTGE) followed by cyclosequencing and RFLP was used to screen almost 90% of the mtDNA, including the control region (CR), for heteroplasmy in 62 children with CVS and neuromuscular disease (CVS+) and in 95 control subjects. One or two rare mtDNA-CR heteroplasmic sequence variants were found in six CVS+ and in zero control subjects (P = 0.003). These variants comprised 6 point and 2 length variants in hypervariable regions 1 and 2 (HV1 and HV2, both part of the mtDNA-CR), one half of which were clustered in the nt 16040-16188 segment of HV1 that includes the termination associated sequence (TAS), a functional location important in the regulation of mtDNA replication. Based upon our findings, sequencing and statistical analysis looking for homoplasmic nucleotide changes was performed in HV1 among 30 CVS+, 30 randomly-ascertained CVS (rCVS), 18 MA, 32 MO, and 35 control haplogroup H cases. Within the nt 16040-16188 segment, homoplasmic sequence variants were three-fold more common relative to control subjects in both CVS groups (P = 0.01 combined data) and in MO (P = 0.02), but not in MA (P = 0.5 vs. control subjects and 0.02 vs. MO). No group differences were noted in the remainder of HV1. We conclude that sequence variation in this small "peri-TAS" segment is associated with CVS and MO, but not MA. These variants likely constitute risk factors for disease development. Our findings are consistent with previous data demonstrating progression of CVS into MO in many cases, and the co-segregation in a maternal inheritance pattern of CVS and MO within families. A mitochondrial component in the pathogenesis of migraine and CVS has therapeutic implications, especially concerning the avoidance of fasting.

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Section: Introductionmentioning

confidence: 78%

Mitochondrial DNA control region sequence variation in migraine headache and cyclic vomiting syndrome

Wang

Ito

Adams

et al. 2004

American J of Med Genetics Pt A

106

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“…Forty years of clinical evidence has suggested that migraine might be attributable to mitochondrial dysfunction (7,31,44,47,48,53,55). Montagna et al and Sangiorgi et al (31,44) both found reduced activity levels of key mitochondrial enzymes in migraineurs.…”

Section: Discussionmentioning

confidence: 96%

Functional mitochondrial analysis in acute brain sections from adult rats reveals mitochondrial dysfunction in a rat model of migraine

Fried

Moffat

Seifert

et al. 2014

American Journal of Physiology-Cell Physiology

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Mitochondrial dysfunction has been implicated in many neurological disorders that only develop or are much more severe in adults, yet no methodology exists that allows for medium-throughput functional mitochondrial analysis of brain sections from adult animals. We developed a technique for quantifying mitochondrial respiration in acutely isolated adult rat brain sections with the Seahorse XF Analyzer. Evaluating a range of conditions made quantifying mitochondrial function from acutely derived adult brain sections from the cortex, cerebellum, and trigeminal nucleus caudalis possible. Optimization of this technique demonstrated that the ideal section size was 1 mm wide. We found that sectioning brains at physiological temperatures was necessary for consistent metabolic analysis of trigeminal nucleus caudalis sections. Oxygen consumption in these sections was highly coupled to ATP synthesis, had robust spare respiratory capacities, and had limited nonmitochondrial respiration, all indicative of healthy tissue. We demonstrate the effectiveness of this technique by identifying a decreased spare respiratory capacity in the trigeminal nucleus caudalis of a rat model of chronic migraine, a neurological disorder that has been associated with mitochondrial dysfunction. This technique allows for 24 acutely isolated sections from multiple brain regions of a single adult rat to be analyzed simultaneously with four sequential drug treatments, greatly advancing the ability to study mitochondrial physiology in adult neurological disorders.

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“…Through this mechanism, GTN could potentially enhance the adenosine signal even when adenosine levels or adenosine receptor expression are not modified. GTN also has multiple effects on mitochondrial function, an organelle that has been suggested to play a role in the development of migraine [27,178,179]. GTN treatment was found to decrease the activity of complex I in the electron transport chain within isolated rat aortas, decreasing oxygen consumption [180].…”

Section: Adenosine and Common Headache Triggersmentioning

confidence: 99%

The Role of Adenosine Signaling in Headache: A Review

2017

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Migraine is the third most prevalent disease on the planet, yet our understanding of its mechanisms and pathophysiology is surprisingly incomplete. Recent studies have built upon decades of evidence that adenosine, a purine nucleoside that can act as a neuromodulator, is involved in pain transmission and sensitization. Clinical evidence and rodent studies have suggested that adenosine signaling also plays a critical role in migraine headache. This is further supported by the widespread use of caffeine, an adenosine receptor antagonist, in several headache treatments. In this review, we highlight evidence that supports the involvement of adenosine signaling in different forms of headache, headache triggers, and basic headache physiology. This evidence supports adenosine A2A receptors as a critical adenosine receptor subtype involved in headache pain. Adenosine A2A receptor signaling may contribute to headache via the modulation of intracellular Cyclic adenosine monophosphate (cAMP) production or 5' AMP-activated protein kinase (AMPK) activity in neurons and glia to affect glutamatergic synaptic transmission within the brainstem. This evidence supports the further study of adenosine signaling in headache and potentially illuminates it as a novel therapeutic target for migraine.

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Mitochondrial Abnormalities in Migraine. Preliminary Findings.

Cited by 67 publications

References 15 publications

Mitochondrial DNA control region sequence variation in migraine headache and cyclic vomiting syndrome

Mitochondrial DNA control region sequence variation in migraine headache and cyclic vomiting syndrome

Functional mitochondrial analysis in acute brain sections from adult rats reveals mitochondrial dysfunction in a rat model of migraine

The Role of Adenosine Signaling in Headache: A Review

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