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早期母婴分离对大鼠成年后再应激及海马神经 可塑性的影响
何静王高华
0
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摘要:
目的 探讨早年母婴分离对大鼠成年后再应激的行为学和神经可塑性的影响。方法 SD大 鼠分为应激抵抗模型组[SRM组,接受早年早期干预应激+成年慢性温和不可预见刺激(CUMS)应激]、 应激敏感模型组(SSM组,接受早年母爱剥夺应激+成年CUMS应激)、CUMS组(仅接受成年CUMS应激), 以及正常对照组(NCM组,不接受任何应激),每组10只。SRM组(每天分离时间15 min)和SSM组(每天分 离时间3 h)从出生第4天开始和母鼠分开,持续一周。成年后第56天评价旷场实验、强迫游泳的行为学 改变。SRM组、SSM组和CUMS组大鼠成年后接受CUMS,持续4周后,再次评价行为学变化,同时免疫组 化比较神经轴突生长和定向分化相关蛋白GAP-43表达变化。结果 早年母婴分离时间长的大鼠(SSM组) 与NCM组大鼠比较,旷场总移动距离减少(F=8.466,P=0.001),中心移动距离减少(F=4.631,P=0.018),强 迫游泳不动时间增加(F=5.201,P=0.012)。母婴分离时间短大鼠(SRM组)与NCM组大鼠相比,差异无统 计学意义(P> 0.05)。成年后再次应激,与NCM组比较,CUMS组总移动距离减少(P=0.041),中心区移动 距离减少(P< 0.001);和CUMS组比较,SSM组旷场总移动距离减少(F=8.868,P< 0.001),中心移动距离 减少(F=13.175,P < 0.001);免疫组化GAP-43表达量SSM组低于NCM组(P < 0.001)。SRM组和NCM组 差异无统计学意义(P> 0.05)。结论 长时间母婴分离使大鼠成年后对应激敏感,GAP-43表达减少,神 经可塑性受到抑制。
关键词:  抑郁  母婴分离  神经可塑性  GAP-43  慢性不可预见温和刺激
DOI:10.3969/j.issn.1009-6574.2017.11.002
基金项目:国家自然科学基金项目( 81571325)
Long term effects of early maternal deprivation on adult rats exposed to chronic unpredictable mildstress and hippocampus neuronal plasticity
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Abstract:
neuronal plasticity when exposed to chronic unpredictable mild stress( CUMS) in adulthood. Methods Litters were randomly assigned to four groups: SSM( stress sensitive group: a daily 3-hour maternal separation + CUMS), SRM( stress resilient group: a daily 15-min maternal separation + CUMS), CUMS( only CUMS) and NCM( normal control group). On Day 4 of parturition, neonatal pups of SRM and SSM group were separated from their mothers for 1 week. Rats were tested in the open field and their immobility time in forced swimming test on PND56( the 56th day of post natal). The adult rats of SRM, SSM and CUMS group were exposed to CUMS for 4 weeks. Then the changes of behaviors were reevaluated, at the same time, immunohistochemistry (IHC) were applied to compare the expression of axonal growth and directional differentiation related protein GAP-43( growth-associated-protein-43). Results Compared with NCM group, SSM group showed decreased total distance( F=8.466, P=0.001) and central distance( F=4.631, P=0.018), and increased forcing swimming time( F=5.201, P=0.012). While there was no statistical significance in the difference between SRM group and NCM group( P> 0.05). In the adulthood stimulation, CUMS group showed decreased total distance( P=0.041) and central distance( P < 0.001) compared to NCM. SSM group showed decreased total distance( F=8.868, P=0.010) and central distance( F=13.175,P< 0.001) compared to the CUMS group. The expression of GAP-43 downregulated for SSM group and CUMS group compared to NCM group after exposed to CUMS( F=9.756,P<0.001). Comapred SRM group with CUMS group, there was no statistical significance. Conclusions Early long time maternal deprivation leads adult rats more vulnerable to stress and downregulate the expression of GAP-43 suppressing neuronal plasticity.
Key words:  Depression  Maternal deprivation  Neuronal plasticity  Growth-associatedprotein- 43  Chronic unpredictable mild stress

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