Efeito do ritmo circadiano alterado no processo epileptogênico

Abstract

Temporal lobe epilepsy (TLE) is a neurological condition characterized by the occurrence of recurrent and spontaneous seizures (SRS). The literature indicates a bidirectional interaction between ELT and the circadian system, considering the oscillatory pattern of epileptic seizures, the influence of circadian rhythm on susceptibility to seizures and the ability of SRS to interfere in the oscillation of other biological rhythms, including sleep-wake, temperature and locomotor activity. In objective to contribute to a better understanding of the relationship between circadian rhythm and epilepsy, the present study investigated the effect of a change in circadian rhythm in the epileptogenic process. We used an ELTM-induced status epilepticus (SE) model to evaluate the effect of different chronic exposures to constant light (LL) on (o): i. susceptibility to SE induced by PILO and the severity of crises during SE; ii. frequency and severity of SRS; iii. temporal distribution of SRS over 24h; iv. 24h rhythm of locomotor activity (SLA). The animals pretreated for two weeks in LL (LL2w) showed an alteration in the SLA rhythm, with an increase in the period (25.01 ± 0.09h) and less relative amplitude - rAMP (0.59 ± 0.028) than the control group (23.94 ± 0.03h; 0.87 ± 0.0039, p <0.0001). The animals pretreated for 7 weeks (LL7w) had the SLA rhythm abolished. The LL2w animals showed a 56% reduction (41.64 ± 3.24) of the total seizures during the SE compared to the control animals (74.48 ± 8.7, p = 0.001); while the LL7w animals showed an increase of 72% (128.25 ± 21.5, p = 0.019) in the total of the crises. However, the treatment of LL for 2w or 7w performed on epileptic animals did not alter the severity of SRS in comparisons before and after treatment. In relation to the temporal distribution of SRS, we observed that LL2w for or LL7w abolished the 24-hour oscillatory pattern. On the other hand, the SLA rhythm, the groups of epileptic animals in conditions of LL presented varied proportions of rhythmic and arrhythmic animals, with a higher proportion of arrhythmic animals in rats exposed to LL7w. The LL epileptic animals that maintained the ALE rhythm has a longer rhythm period (25.65 ± 0.3h) than the LD epileptic group (24.91 ± 0.43, p <0.0001). A decrease in the rAMP of the LL groups was observed, being less stable and more fragmented than the control group. There was a significant reduction in rAMP in the epileptic group LL2w (0.14 ± 0.031, p <0.0001) and LL7w (0.35 ± 0.06, p = 0.01), in relation to the epileptic group LD (0.63 ± 0.068). Constant light for a long time causes disruptions at different biological rhythms and may lead to an interruption of the oscillatory pattern. In our study, the rhythm of SLA as well as SRS is altered in animals exposed to LL. The LL epileptic animals that maintained the SLA rhythm, showed a very weak and unstable rhythm. The data set suggests that rhythm control mechanisms are associated with the rhythmicity of limbic seizures and the susceptibility of crises during SE. The characterization of the temporal oscillation of molecules involved in pro-convulsive or anti-convulsive pathways associated with SE induction may contribute to the understanding of the effect of constant light in the acute phase of the epileptogenic process. Furthermore, the study indicates that SRS, per se, alter the rhythm of SLA and that this alteration is aggravated in constant light and condition, possibly due to a combined effect of epileptic activity and light on the control system of the rhythm.