Kim Chea-Ha, Park Soo-Hyun, Sim Yun-Beom, Sharma Naveen, Kim Sung-Su, Lim Su-Min, Jung Jun-Sub, Suh Hong-Won
Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, 39 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702, Republic of Korea.
Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, 39 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702, Republic of Korea.
Neurosci Res. 2014 Dec;89:31-6. doi: 10.1016/j.neures.2014.08.017. Epub 2014 Sep 10.
The effect of cholera toxin (CTX) or pertussis toxin (PTX) administered supraspinally on hippocampal neuronal cell death in CA3 region induced by kainic acid (KA) was examined in mice. After the pretreatment with either PTX or CTX intracerebroventricularly (i.c.v.), mice were administered i.c.v. with KA. The i.c.v. treatment with KA caused a neuronal cell death in CA3 region and PTX, but not CTX, attenuated the KA-induced neuronal cell death. In addition, i.c.v. treatment with KA caused an elevation of the blood glucose level. The i.c.v. PTX pretreatment alone caused a hypoglycemia and inhibited KA-induced hyperglycemic effect. However, i.c.v. pretreatment with CTX did not affect the basal blood glucose level and KA-induced hyperglycemic effect. Moreover, KA administered i.c.v. caused an elevation of corticosterone level and reduction of the blood insulin level. Whereas, i.c.v. pretreatment with PTX further enhanced KA-induced up-regulation of corticosterone level. Furthermore, i.c.v. administration of PTX alone increased the insulin level and KA-induced hypoinsulinemic effect was reversed. In addition, PTX pretreatment reduces the KA-induced seizure activity. Our results suggest that supraspinally administered PTX, exerts neuroprotective effect against KA-induced neuronal cells death in CA3 region and neuroprotective effect of PTX is mediated by the reduction of KA-induced blood glucose level.
在小鼠中检测了脊髓以上给予霍乱毒素(CTX)或百日咳毒素(PTX)对海人酸(KA)诱导的CA3区海马神经元细胞死亡的影响。在脑室内(i.c.v.)预先给予PTX或CTX后,给小鼠脑室内注射KA。脑室内注射KA导致CA3区神经元细胞死亡,而PTX而非CTX减轻了KA诱导的神经元细胞死亡。此外,脑室内注射KA导致血糖水平升高。单独脑室内注射PTX预处理导致低血糖,并抑制KA诱导的高血糖效应。然而,脑室内预先给予CTX不影响基础血糖水平和KA诱导的高血糖效应。此外,脑室内注射KA导致皮质酮水平升高和血液胰岛素水平降低。而脑室内预先给予PTX进一步增强了KA诱导的皮质酮水平上调。此外,单独脑室内注射PTX增加了胰岛素水平,KA诱导的低胰岛素血症效应被逆转。此外,PTX预处理降低了KA诱导的癫痫发作活动。我们的结果表明,脊髓以上给予PTX对KA诱导的CA3区神经元细胞死亡具有神经保护作用,且PTX的神经保护作用是通过降低KA诱导的血糖水平介导的。