Non-adenosine nucleosides and absence epilepsy

What is it about?

Both GABAergic system and glutamatergic system are involved in the pathomechanism of absence epilepsy, the lipopolysaccharide(LPS)-evoked increase in absence epileptic activity and the pro- or antiepileptic effects of non-adenosine (non-Ado) nucleosides inosine (Ino), guanosine (Guo) and uridine (Urd). Moreover, Ino, Guo and Urd have modulatory effects on inflammatory processes. Thus, we investigated whether Ino, Guo and Urd have also modulatory influence on LPS-evoked increase in spike-wave discharge (SWD) number using two different concentrations of each nucleoside in absence epileptic Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. We demonstrated that Ino dose-dependently aggravated whereas Guo and Urd attenuated the LPS-evoked increase in SWD number. Our results suggest that different nucleosides have diverse effects on LPS-induced changes in absence epileptic activity.

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Why is it important?

Despite the accumulating evidence on antiinflammatory and antiepileptic effects of non-Ado nucleosides and on relations between inflammation and epileptogenesis there is a little information on the modulatory effect of non-Ado nucleosides on neuroinflammatory processes in the CNS. We demonstrated that Ino aggravated but Guo and Urd alleviated the LPS-induced increase in SWD number possibly via modulation of cortical hyperexcitability: Ino may increase it by activation/enhancement of the functioning of Ado/A2ARs/IL-1β system whereas Guo and Urd may diminish it by reduction of the level of proinflammatory cytokines. In relation to the LPS-evoked absence epileptic activity changes, our results suggest a crosstalk between LPS-induced TLR4/IL-1R/proinflammatory cytokine system, glutamatergic system, GABAergic system and adenosinergic system, in which processes non-Ado nucleosides may have modulatory functions.

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