Vitamin E reduces spasms caused by prenatal stress by lowering calpain expression

• Published in: Epilepsy & behavior 2021-01, Vol.114 (Pt A), p.107609-107609, Article 107609
• Main Authors: Kwon, Hyeok Hee, Lee, Jin-Seok, Park, Hyewon, Shin, Juhee, Yin, Yuhua, Shin, Nara, Shin, Hyo Jung, Hwang, Jeong-Ah, Kim, Dong Woon, Kang, Joon Won
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Calpain; Catalase - metabolism; Female; GABA; Glutathione - metabolism; Infantile spasms; Oxidative Stress; Pregnancy; Prenatal stress; Rats; Rats, Sprague-Dawley; Seizure; Spasm; Superoxide Dismutase - metabolism; Vitamin E; Vitamin E - therapeutic use
• ISSN: 1525-5050; 1525-5069
• DOI: 10.1016/j.yebeh.2020.107609

[Display omitted] •Vitamin E reduced susceptibility to N-methyl-D-aspartate (NMDA)-induced spasms in prenatally stressed rats.•Vitamin E rescued K+/Cl− co-transporter (KCC2), glutamate decarboxylase (GAD67), and calpain expressions in prenatally stressed rats.•Dihydroethidium (DHE), malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), glutathione (GSH)/GSH/glutathione disulfide (GSSG), and catalase -mediated reactive oxygen species (ROS) decreased in the treated rats. Prenatal stress increases the susceptibility of infants to seizures and is known to be associated with oxidative stress. Recent studies suggest that vitamin E has beneficial effects in various neurological diseases due to its antioxidant properties. In this study, we investigated the relationship between prenatal stress and vitamin E treatment on N-methyl-D-aspartate (NMDA)-induced spasms. We used pregnant female Sprague Dawley rats and induced prenatal stress with an injection of betamethasone on G15. They were then treated orally with 200 mg/kg vitamin E or saline twice a day from G15–G21. On postnatal day 15, NMDA was administered to trigger spasms in offspring. The total number of spasms and latency to the first spasm were recorded. We also measured oxidative stress in the medial cortex using western blot, and calpain activity, thiobarbituric acid reactive substances (TBARS), glutathione (GSH)/GSH/glutathione disulfide (GSSG), superoxide dismutase (SOD) activity, catalase activity, and nitric oxide (NO) assays. We observed that rats treated with vitamin E while exposed to prenatal stress demonstrated reduced total number and frequency of spasms. Expression of glutamate decarboxylase 67 (GAD67) and K+/Cl− co-transporter (KCC2) were reduced after prenatal stress; this recovered in the vitamin E treated group. Further, expression of calpain 2 was decreased and various markers of oxidative stress (malondialdehyde (MDA), GSH/GSSG, SOD, catalase, and NO) were reduced in the vitamin E treated group. Our results provide evidence that vitamin E lowers oxidative stress and decreases seizure susceptibility in rat offspring exposed to prenatal stress. Given the well-known safety profile of vitamin E, these results indicate its potential as a strategy for preventing seizures.