Acute intermittent hypoxia induces hypoglossal nerve metaplasticity in a 5-HT2A R-activated protein kinase C dependent manner in chronic intermittent hypoxia-pretreated rats

作者：Wang, Nian; Tu, Xueping; Hu, Ke^*; Chen, Hongbin; Xianyu, Yunyan; Cao, Xia; Kang, Jing; He, Jingya; Zhao, Pengzhan; Mei, Yongtian

来源：International Journal of Clinical and Experimental Medicine, 2016, 9(6): 12175-12188.

• Acute intermittent hypoxia
• chronic intermittent hypoxia
• long term facilitation
• hypoglossal nerve
• frequency long-term facilitation
• amplitude long-term facilitation

Objective: This study was to explore whether the acute intermittent hypoxia (AIH) induced hypoglossal nerve discharge metaplasticity was dependent on 5-HT2A R-activated PKC (PKC.) in chronic intermittent hypoxia (CIH)-pretreated rats. Methods: Twenty-nine Sprague-Dawley rats were pretreated with CIH before AIH for 3 consecutive weeks. The frequency and average peak amplitude of hypoglossal nerve discharges were then recorded and compared before and after intravenous injection of saline (control group, n=6), ketanserin tartrate (a selective antagonist of 5-HT2A receptors, 2 mg/kg, n=8), PKC theta-pseudosubstrate (40 mu g/kg, n=8) or ketanserin tartrate combined with PKC theta-pseudosubstrate (n=7). Another 15 rats without CIH-pretreatment were randomly divided into 3 normoxia exposure groups: normoxia-treated rats without AIH exposure as time controls (n=5), normoxia-treated rats with AIH exposure (n=5) and normoxia-treated rats with ketanserin and PKC theta-pseudosubstrate injection (n=5). Results: AIH induced a sustained elevation of hypoglossal nerve activities characterized by long-term facilitation (LTF) in spontaneously breathing, vagotomized and anesthetized, CIH-pretreated rats. The increase in CIHpretreated rats was significantly higher than innormoxia-treated rats. CIH-induced plasticity by AIH occurred through increasing hypoglossal frequency. Compared with control group, the frequency and average amplitude increased less in ketanserin group, whereas they significantly decreased in both PKC theta-pseudosubstrate group and ketanserin combined with PKC theta-pseudosubstrate group. Conclusion: Our results indicated that CIH strengthened the AIH induced hypoglossal plasticity primarily via increasing hypoglossal frequency, and 5-HT2A R-activated PKC (PKC.) in the hypoglossal neurons may modulate the AIH induced hypoglossal nerve plasticity in CIH-pretreated rats.

• 出版日期2016
• 单位武汉大学