Elevated body temperature affects spike-and-wave discharges and induces behavioural deficits in genetic absence epilepsy rats.

PURPOSE: A mild decrease in body temperature has been linked to spike-and-wave discharges (SWDs) in absence seizure models, suggesting hypothermia as a trigger. This study examined if elevated body temperature affects SWDs, anxiety-like behaviour, and locomotion in genetic absence epilepsy rats from Strasbourg (GAERS).

MATERIALS AND

METHODS

Electroencephalogram (EEG) recordings, elevated plus maze or locomotor activity tests were performed at room-temperature (basal levels) and high-ambient temperature via heat-cabinet (1 h each session) in 4-5-month-old-male GAERS (n = 11). Mean and cumulative duration and total number of SWDs were reckoned, and the spectral characteristics of the SWDs were analyzed by computing power spectra using Fast Fourier Transform. Elevated plus maze and locomotor activity tests were used to assess anxiety-like behaviour and locomotion. The results were compared by paired-t and Wilcoxon tests; Pearson correlation (GraphPad-Prism-10.1.1). The significance level was set at p < 0.05. Data were expressed as box-and-whisker plots or mean±SEM.

RESULTS

Mean body temperature increased (p = 0.0003) following heat-exposure (39.8 ± 0.4 °C) compared to basal-level (37.9 ± 0.1 °C). Heat-exposure reduced mean (sec, Basal:14.5 ± 0.9, Cabinet:12.3 ± 0.6, p = 0.0256) and cumulative SWD duration (sec, Basal:1269 ± 110.4, Cabinet:806.4 ± 60, p = 0.0113) compared to baseline. The peak frequency of SWDs increased under the heat-cabinet condition compared to room temperature (Hz, 7.9 ± 0.1 vs. 7.4 ± 0.1, p = 0.0156). Rats spent less time in open arms (% time; Basal:15.9 ± 4.1, Cabinet:3.6 ± 1.1, p = 0.0204) and showed decreased locomotion (p < 0.05). Significant negative correlation was found between body temperature and mean SWD duration (r = -0.763; p = 0.01) and between time spent in the open arm and mean SWD duration (r = -0.687; p = 0.028).

CONCLUSION

The increase in body temperature is associated with shorter duration of absence seizures, reduced locomotor activity, and anxiety-like symptoms in GAERS, suggesting thermoregulatory pathways may be involved in seizures and comorbidities. This may influence how people with absence epilepsy react to elevated temperatures, for example during heat waves.