Summary Objective The DBA/1 mouse is a relevant animal model of sudden unexpected death in epilepsy (SUDEP), as it exhibits seizure-induced respiratory arrest (S-IRA) evoked by acoustic stimulation, followed by cardiac arrhythmia and death. Defects in serotonergic neurotransmission may contribute to S-IRA. The tryptophan hydroxylase-2 (TPH2) enzyme converts L-tryptophan to 5-hydroxytryptophan (5-HTP), a precursor for central nervous system (CNS) serotonin (5-HT) synthesis; and DBA/1 mice have a polymorphism that decreases TPH2 activity. We, therefore, hypothesized that supplementation with 5-HTP may bypass TPH2 and suppress S-IRA in DBA/1 mice. Methods TPH2 expression was examined by Western blot in the brainstem of DBA/1 and C57BL/6J mice both with and without acoustic stimulation. Changes in breathing and cardiac electrical activity in DBA/1 and C57BL/6J mice that incurred sudden death during generalized seizures evoked by pentylenetetrazole (PTZ) were studied by plethysmography and electrocardiography. The effect of 5-HTP administration on seizure-induced mortality evoked by acoustic stimulation or by PTZ was investigated in DBA/1 mice. Results Repetitive acoustic stimulation resulted in reduced TPH2 protein in the brainstem of DBA/1 mice as compared with C57BL/6J mice. S-IRA evoked by acoustic stimulation in DBA/1 mice was significantly reduced by 5-HTP. Following S-IRA, cardiac electrical activity could be detected for minutes before terminal asystole and death in both DBA/1 and C57BL/6J mice after PTZ treatment. The incidence of S-IRA by PTZ administration was greater in DBA/1 than in C57BL/6J mice, and administration of 5-HTP also significantly reduced S-IRA by PTZ in DBA/1 mice. Significance Our data suggest that S-IRA is the primary event leading to death incurred in most DBA/1 and some C57BL/6J mice during PTZ-evoked seizures. Suppression of S-IRA by 5-HTP suggests that 5-HT transmission contributes to the pathophysiology of S-IRA, and that 5-HTP, an over-the-counter supplement available for human consumption, may be clinically useful in preventing SUDEP.

ERA-Interim has been widely considered as a valid proxy for observations at global and regional scales. However, the verifications of ERA-Interim precipitation and temperature in mainland China have been rarely conducted, especially in the spatial and long-term performances. Therefore, in this study, we employed the interpolated ground station (STA) data to evaluate the spatial and temporal patterns and trends of ERA-Interim precipitation and temperature during 1980–2012. The results showed that relatively weaker performances were observed in ERA-Interim precipitation, with the skill score (S index) ranging from 0.41 to 0.50. Interannual ERA-Interim precipitation presented comparable trends with STA precipitation at the annual and seasonal scales. Spatial patterns of empirical orthogonal function (EOF) modes and corresponding principal components were evidently different between annual ERA-Interim and STA precipitation. For temperature, annual and seasonal patterns of ERA-Interim data were in good consistency with those of STA over China with the S index ranging from 0.59 to 0.70. Yet interannual STA temperature recorded stronger warming trends (from 0.37 K decade−1 of wintertime to 0.53 K decade−1 of springtime) at the annual and seasonal scales compared to corresponding periods for ERA-Interim temperature (from 0.03 K decade−1 of wintertime to 0.25 K decade−1 of summertime). Overall, ERA-Interim precipitation and temperature had good agreement with STA data in east China with lower elevation (<1000 m above sea level), but good agreements were not observed in west China with higher elevation. The findings suggest that caution should be paid when using ERA-Interim precipitation and temperature in areas with complex orography.