HİPOKRETİN NÖRONLARININ ABSANS EPİLEPSİ İLE İLİŞKİSİNİN ARAŞTIRILMASI

Objective: In the absence epilepsy, seizures usually occur during the transition to sleep and the period of passive wakefulness. Hypocretin (orexin) is an important neurotransmitter involved in sleep-wake regulation. The role of orexin in the absence epilepsy is not fully understood. Our aim in this study is to uncover the effect of orexinergic modulation on the absence epilepsy and the contribution of GABA, glutamic acid, serine, and glycine to this possible effect.

Methods: In our study, experimental and control groups were formed with 11-month-old male Wistar and WAG/Rij rats (n=6). In all animals, microdialysis cannulas were placed in the perioral region of the somatosensory cortex (Spo1), and epidural tripolar electrodes. In the study, first an orexin agonist (orexin A, IN) and then a dual orexin receptor antagonist (i.p. filorexant, DORA) was administered and its effects on seizures were evaluated. Levels of GABA, glutamic acid, glycine, and serine were measured in cerebrospinal fluid samples taken at 30-minute intervals. Seizure activity was assessed from concurrent EEG recordings.

Results: A time-dependent decrease in absence seizures was found (p < 0.05). While convulsive seizures developed in WAG/Rij rats, this was not observed in Wistars. Although there was a significant positive correlation between GA, GABA, glycine, and serine levels measured in the Spo1 region (p < 0.0001), the correlation wasn't found with the absence seizure parameters. The increase in GA, glycine, and serine levels in the WAG- Rij control group compared to the experimental group after the application of the antagonist/solvent was statistically significant (p < 0.001). A negative correlation was found between absence and convulsive seizures (p < 0.05).

Conclusion: In light of all these results, possible factors underlying the absence seizures, and time-dependent changes in amino acid neurotransmitter levels were discussed. The contribution of the orexinergic system, the development of convulsive seizures, and physicochemical processes were evaluated. New studies are needed to better understand the mechanism of absence epilepsy.