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Background <p>Migraine is a disabling neurovascular disorder in which neuroinflammation, trigeminal activation, and mitochondrial dysfunction play central roles. Mitochondria-targeted antioxidants such as mitoTEMPO may modulate these mechanisms; however, their effects in nitroglycerin (NTG)–induced migraine models remain unclear. This study investigated the effects of mitoTEMPO on mitochondrial biogenesis, fusion–fission dynamics, trigeminal activation, and inflammation in the trigeminal ganglion in an NTG-induced migraine model.</p> Methods and results <p>Thirty male Sprague–Dawley rats were allocated to control, mitoTEMPO (M), NTG, M + NTG (concomitant administration of mitoTEMPO with NTG), and NTG + M (delayed administration of mitoTEMPO following NTG exposure) groups (<i>n</i> = 6/group). Serum TNF-α levels were measured by ELISA; trigeminal c-Fos, mitofusin-1 (Mfn1), nuclear respiratory factor (NRF1), and mitochondrial transcription factor A (TFAM) protein levels were assessed by Western blot, while NADH-ubiquinone oxidoreductase chain 1 (ND1), TFAM, NRF1, Mfn1, and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) mRNA expressions were analyzed by RT-PCR. NTG administration significantly increased serum TNF-α levels and trigeminal c-Fos expression, confirming neuroinflammation and nociceptive activation. Concomitant mitoTEMPO administration attenuated c-Fos expression, whereas delayed administration had no effect, indicating a timing-dependent response. Compared with the NTG group, mitoTEMPO-treated NTG groups exhibited higher Mfn1, NRF1, and TFAM protein levels. At the transcriptional level, no differences were observed in ND1, TFAM, or NRF1 expression; however, Mfn1 mRNA was increased in the NTG group, and PGC-1α expression was significantly upregulated in the NTG + M group, consistent with a delayed mitochondrial biogenesis response.</p> Conclusions <p>These findings suggest that NTG induces trigeminal activation and inflammation with limited acute effects on mitochondrial biogenesis, while mitoTEMPO modulates these processes in a phase-dependent manner.</p>

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MitoTEMPO modulates trigeminal activation and mitochondrial biogenesis in a nitroglycerin-induced migraine model

  • 期刊论文

  • 发表日期：

    2026年5月11日

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  • Ozgur Yildirim Savran,
  • Simay Alcan-Kirtas,
  • Ozbeyen Atalay,
  • Hasan Basri Kilic,
  • Meltem Tuncer

摘要

Background

Migraine is a disabling neurovascular disorder in which neuroinflammation, trigeminal activation, and mitochondrial dysfunction play central roles. Mitochondria-targeted antioxidants such as mitoTEMPO may modulate these mechanisms; however, their effects in nitroglycerin (NTG)–induced migraine models remain unclear. This study investigated the effects of mitoTEMPO on mitochondrial biogenesis, fusion–fission dynamics, trigeminal activation, and inflammation in the trigeminal ganglion in an NTG-induced migraine model.

Methods and results

Thirty male Sprague–Dawley rats were allocated to control, mitoTEMPO (M), NTG, M + NTG (concomitant administration of mitoTEMPO with NTG), and NTG + M (delayed administration of mitoTEMPO following NTG exposure) groups (n = 6/group). Serum TNF-α levels were measured by ELISA; trigeminal c-Fos, mitofusin-1 (Mfn1), nuclear respiratory factor (NRF1), and mitochondrial transcription factor A (TFAM) protein levels were assessed by Western blot, while NADH-ubiquinone oxidoreductase chain 1 (ND1), TFAM, NRF1, Mfn1, and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) mRNA expressions were analyzed by RT-PCR. NTG administration significantly increased serum TNF-α levels and trigeminal c-Fos expression, confirming neuroinflammation and nociceptive activation. Concomitant mitoTEMPO administration attenuated c-Fos expression, whereas delayed administration had no effect, indicating a timing-dependent response. Compared with the NTG group, mitoTEMPO-treated NTG groups exhibited higher Mfn1, NRF1, and TFAM protein levels. At the transcriptional level, no differences were observed in ND1, TFAM, or NRF1 expression; however, Mfn1 mRNA was increased in the NTG group, and PGC-1α expression was significantly upregulated in the NTG + M group, consistent with a delayed mitochondrial biogenesis response.

Conclusions

These findings suggest that NTG induces trigeminal activation and inflammation with limited acute effects on mitochondrial biogenesis, while mitoTEMPO modulates these processes in a phase-dependent manner.