神经营养因子对大鼠学习记忆及海马一氧化氮合酶阳性神经元数目的影响

背景:神经营养因子在神经系统发育和正常生理功能维持及神经损伤中起着重要的作用。对神经营养因子的研究是目前神经科学领域的热点和前沿课题之一。目的:研究脑室内注射脑源性神经营养因子(brain-derivedneurotrophicfactor,BDNF)抗体阻断内源性BDNF对大鼠海马一氧化氮合酶(nitricoxidesynthase,NOS)阳性神经元数目的影响。设计:随机对照的实验研究。地点和对象:实验地点在中山大学基础医学院脑研究室。实验对象为健康雄性SD大鼠13只。干预:大鼠脑室内注射BDNF抗体一周后,采用Morris水迷宫进行行为检测。主要观察指标:观察大鼠定位航行试验和空间探索试验状况,并用NADPH-黄递酶组化染色方法观察海马NOS阳性神经元数目的变化。结果:定位航行试验:实验组大鼠平均逃避潜伏期为(33.46±2.64)s,对照组为(17.71±1.86)s,两者差异具有非常显著性意义(t=4.8733,P<0.01);空间探索试验:实验组大鼠在平台象限游泳距离百分比为(28.89±6.31)%,对照组为(41.99±7.46)%,实验组明显低于对照组(t=3.3907,P<0.01);与对照组相比,实验组大鼠空间学习和记忆能力明显下降。实验组大鼠海马CA1区NOS阳性神经元数目(38.37±5.23)明显少于对照组(49.53±5.74)(t=8.200,P<0.01);实验组DG区NOS阳性神经元数目(48.77±5.51)明显少于

Impact of neurotrophicfactor on learning and memory as well as the number of hippocampal nitric oxide synthasepositive neurons in rats

BACKGROUND: Neurotrophic factor(NF) plays an important role in the development of nervous system, the maintenance of normal physiological function and neural injury. It is one of the hotspots and advanced topics in neurology field to investigate NF at present.OBJECTIVE: To investigate the impact of brain-derived NF(BDNF) antibody injected into cerebral ventricle to block endogenous BDNF on the number of hippocampal nitric oxide synthase(NOS) positive neurons.DESIGN: A randomised controlled trial.SETTING and PARTICIPANTS: Study was conducted in the brain institute of the Elementary Medicine College of Sun Yat-sen University. Thirteen healthy male SD rats were selected in the study.INTERVENTIONS: Morris water maze to test the animal behaviour at one week after the injection of BDNF antibody into the cerebral ventricle of the rats.MAIN OUTCOME MEASURES: The condition of location and navigation tests and the spatial exploring test was observed as well as the alteration of the hippocampal NOS positive neuron numbers after NADPH-diaphorase histochemical staining.RESULTS: Location and navigation test: mean escape latency of the rats in study group was(33.46±2.64) s, which was significantly longer than (17.71 ± 1.86) s of control group( t =4. 873 3, P ＜ 0. 01) . Spatial exploring test: the percentage of swimming adistance in flat quadrant in rats of study group was(28.89 ±6. 31)% , which was significantly lower than (41.99±7.46)% of control group ( t = 3. 390 7, P ＜0.01) .The spatial study and memory of the rats in study group significantly decreased compared with that of control group. The NOS positive neuron number in hippocampal CA1 region was(38.37 ±5.23), which was significantly less than(49.53 ± 5.74) of control group( t = 8. 200, P ＜ 0. 01 ) . NOS positive neuron numbers of DG region in study group was(48.77 ±5.51), which was significantly less that (60. 40 ± 7.39) of control group ( t = 7.091, P ＜ 0. 01 ).CONCLUSION: The injection of BDNF antibody into cerebral ventricle could induce reduction in the ability of spatial learning and memory in rats as well as the reduction in hippocampal NOS positive neuron numbers, which indicate the impact of BDNF on learning and memory might relate with the alteration of the hippocampal NOS positive neuron numbers.