慢性睡眠剥夺对大鼠空间学习记忆、海马体齿状回区去甲肾上腺素水平及其受体表达的影响

Effects of chronic sleep deprivation on abilities of spatial learning and memory and norepinephrine level and its receptor expression in hippocampal dentate gyrus in rats

目的探讨慢性睡眠剥夺(CSD)对大鼠空间学习记忆和海马体齿状回区(DG)去甲肾上腺素(NE)水平及其受体表达的影响,初步阐明CSD影响空间学习记忆能力的神经化学机制。方法将大鼠设为CSD组及对照组(每组8只),应用睡眠剥夺仪进行睡眠剥夺(18 h/d,连续21 d)。Morris水迷宫检测2组大鼠行为能力的改变情况。脑部微量透析法和高效液相色谱法检测DG区去甲肾上腺素(NE)水平,α1和β肾上腺素能受体(α1-AR和β-AR)表达应用免疫组织化学染色法检测。结果 CSD组大鼠第2、3 d游到平台所用时间为(75.76±17.15)和(37.60±4.80)s,均高于对照组;第5天穿越原站台区域回数比较,CSD组[(3.25±1.25)次]与对照组[(8.00±1.82)次]比较,差异有统计学意义(P<0.05);第2~4天CSD组大鼠DG区内NE水平分别为(285.82±75.56)%、(409.10±134.91)%、(503.27±185.87)%,对照组分别为(601.41±36.96)%、(1 235.71±132.11)%、(1 085.41±188.21)%,差异均有统计学意义(均P<0.05);α1-AR和β-AR表达评分在对照组分别为4.66±0.28和5.00±0.33,在CSD组大鼠分别为2.50±0.45和2.75±0.43,2组α1-AR和β-AR表达评分比较,差异均有统计学意义(均P<0.05)。结论 CSD可损害大鼠空间学习和记忆能力,可能与海马体DG区NE水平降低及其受体表达减少有关。

Objective To investigate the effects of chronic sleep deprivation(CSD) on abilities of spatial learning and memory, and norepinephrine(NE) level and its receptor expression in hippocampal dentate gyrus(DG) in rats, clarify the neurochemical mechanism of CSD in affecting spatial learning and memory. Methods The rats were divided into CSD group and control group(8 in each group),and sleep deprivation was performed by the sleep deprivation instrument for consecutive 21 days(18 h/d). The change in behavior ability of two groups was detected by Morris water maze. The NE level in DG was determined by brain microdialysis and high performance liquid chromatography. The expressions of α1 and β adrenergic receptor (α1-AR and β-AR) were measured by immunohistochemical staining. Results The time of swimming to the platform in the second and third day of the CSD group was(75.76±17.15) and(37.60±4.80) s respectively, which both were higher than those of the control group. In the fifth day, there was statistically significant difference in the number of crossing the original platform between the CSD group[(3.25±1.25)times]and the control group [( 8. 00 ± 1. 82) times ]( P < 0. 05). In the second to fourth day, the NE level in DG in the CSD group was respectively(285.82±75.56)%,(409.10±134.91)% and(503.27±185.87)%, while that in the control group was(601.41±36.96)%,(1235.71±132.11)% and(1085.41±188.21)% respectively, and the differences were statistically significant(all P<0.05). The score of α1-AR and β-AR expression in the control group was 4.66±0.28 and 5.00±0.33 respectively, while that in the CSD group was2.50 ±0.45 and 2.75 ±0.43 respectively, and the differences in the scores of α1-AR and β-AR expression were statistically significant between the two groups(all P<0.05). Conclusion CSD can impair the spatial learning and memory ability in rats, which may be related to the decrease of NE level and its receptor expression in the hippocampal DG.