Glikojen Döngüsünün Bozulmasının Kortikal Yayılan Depolarizasyon Oluşumu ve Panneksin 1 Kanalları Üzerine Etkisinin Araştırılması
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Migraine is an episodic neurological disorder that affects 10-20 % of general population. Cortical spreading depression (CSD) is proposed as the mechanism of migraine aura and the downstream trigeminal activation as the mechanism of migraine headache. Hunger and sleep deprivation are trigger factors for migraine. The mechanism underlying these triggers could be related to glycogen turnover since astrocytic glycogen stores can be used as a source of energy especially during intense glutamatergic neurotransmission as those events require the maintenance of low extracellular glutamate and K+ concentrations around synapses. Glycogen turnover is regulated by synthesis and degradation enzymes called glycogen synthase and glycogen phosphorylase, respectively as well as glucose concentration in astrocytes. We hypothesized that alteration of the glycogen synthase activity with extended wakefulness, inhibition of glycogen phosphorylase by DAB and restriction of glucose influx to astrocytes by phloretin could interfere with glycogen turnover. Our attempts that restrict the utilization of glycogen decreased CSD threshold and this decreased threshold recovered when the animal was superfused with energy substrates L-lactate and D-glucose. Recently, it was shown that pannexin1 hemi-channels are activated during CSD, high K+ and/or glutamate and low extracellular glucose levels. We also investigated the effect of impaired glycogen turnover on pannexin1 hemi-channels and found that intense somatosensory stimulus activates pannexin1 hemi-channels during impaired glycogen turnover. In conclusion, our data is consistent with our hypothesis that glycogen may be required for preventing CSD generation and conditions that compromise glycogen use such as extended wakefulness, DAB and intense synaptic activation could lead to pannexin channel activation and therefore migraine attacks.