断乳前丰富环境暴露促进大鼠学习记忆及海马神经发生

Preweaning exposure to enriched environment promote hippocampal function and neurogenesis in rats

目的探讨断乳前丰富环境（Enriched environment）暴露对大鼠空间记忆和海马神经发生的影响。方法新生大鼠随机分为对照组和丰富环境组,丰富环境组大鼠每日予以丰富环境暴露20min。50d龄开始用Morris水迷宫测试空间学习记忆能力。采用BrdU标记增殖细胞,观察2组海马神经发生情况,并对海马神经发生与Morris水迷宫测试成绩作相关分析。结果丰富环境组Morris水迷宫成绩优于对照组,差异均有显著性（均P〈0.05）。丰富环境组大鼠海马区BrdU阳性细胞数[（5363±487）个]、神经元分化率[（85.0±2.8）%]和星形胶质细胞分化率[（4.0±0.5）%]均高于对照组[分别为（2984±318）个,（80.2±2.8）%,（2.6±0.6）%]（均P〈0.01）。相关分析显示对照组海马DG区新生神经元数目与Morris水迷宫测试成绩相关（r=0.648,0.609,P〈0.05）,但在丰富环境组中相关性消失。结论断乳前丰富环境暴露可以促进海马神经发生和海马功能。丰富环境暴露在新生期或幼年期脑损伤康复治疗中可能有良好的应用前景。

Objective To explore the effects of preweaning exposure to enriched environment on hippocampal function and neurogenesis in rats. Methods Twenty-four 10-day-old SD rats were randomly divided into the Control group and Enriched environment group （ EE group）, 12 for each group, Since 10 day-old to 24 days, each rat received intraperitoneal injections of BrdU （50 mg/kg each ） every two days to label newly proliferated cells in vivo, and rats in EE group were daily exposed to enriched environment for 20 minutes：, All rats were subjected to hidden platform trials and a probe trial in Morris water maze since 50 day-old, and were sacrificed at age of 63 days. Coronal cryostat sections were cut. BrdU immunohistochemistry and double immunofluorescence （ BrdU/NeuN or BrdU/GFAP） were done, and numbers of BrdU-labeled cells and ratios of neurons and astrocytes differentiated from BrdU-labeled cells were calculated. Results Repeated measure ANOVA over 12 blocks of hidden platform trials showed latencies of EE group were significantly shorter than those of Control group （ F= 5. 155, P = 0.032）. After 6 days hiatus, a probe trial was administered where the platform was removed. The rats in EE group spent more time in the quadrant where the platform were used to be, compared with control rats [ （63 ± 11 ） % vs （52 ± 11 ） %, t = 2.601, P = 0. 016 ]. As compared with Control group, number of BrdU labeled cells [ （5363 ± 487） vs （2984 ± 318）, t = 14. 177, P 〈 0.01 ], and ratios of neurons [ （85.0 ± 2.8 ） % vs （ 80.2 ± 2.8）%,t=4.166, P〈0.01] andastrocytes [（4.0±0.5）% vs （2.6±0.6）%,t=6.493, P〈0.01] were higher in EE group. Pearson5 analysis found that the number of newborn neurons in DG area positively correlated with the test results of Morris water maze in the Control group, but not in the EE group. Conclusion Preweaning exposure to enriched environment can promote hippocampal function and neurogenesis, which suggest it may be a promising treatment for brain damage during neonatal or juvenile period.