Medical Psychological Research Center, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
Behav Brain Res. 2010 Jun 19;209(2):281-8. doi: 10.1016/j.bbr.2010.02.005. Epub 2010 Feb 6.
In this study we investigated the effects of maternal deprivation on adult rats' spatial learning and memory, exploratory, and limbic activity and their correlations with the gene expression of dopamine transporter (DAT) and dopamine D1, D2, D3 receptors (DRD1, DRD2, DRD3) in the nucleus accumbens (NAc). We further investigated whether DNA methylation is involved in the regulation of DRD2 gene expression. Results from our behavioral tests demonstrated that maternal deprivation significantly decreased the spatial learning and memory ability, exploratory ability, and limbic activity in adult rats, while results from our molecular analysis revealed that the mRNA levels of DAT, DRD1, DRD2, and DRD3 were significantly downregulated in maternally deprived rats in comparison to control animals. Correlation analysis in the maternally deprived rats suggested that downregulated DAT and DRD2 mRNA levels significantly correlated with the amount of time required to find the platform, but only DRD2 significantly correlated with the time spent in target quadrant in the Morris water-maze test; DAT, DRD1 and DRD2 mRNA levels significantly correlated with the number of vertical activity, but only DRD2 mRNA level significantly correlated with total distance in the open field test. Conversely, DRD3 mRNA level did not display any correlation with behavioral changes. The methylated CpG levels in the promoter region of DRD2 gene and the expression of DNA methyltransferases 1 (Dnmt1) and 3alpha (Dnmt3alpha) were not significantly changed in maternal deprivation group in comparison to the control group. We concluded that downregulation of DAT, DRD1 and DRD2 gene expression in the NAc is in response to the abnormality in exploratory behaviors; downregulation of DAT and DRD2 expression is in response to the abnormality in spatial learning; downregulation of DRD2 is in response to the abnormality in the spatial memory in maternally deprived rats; whereas DRD3 plays no role in these behaviors. DNA methylation might not be the mechanism to regulate the mRNA level.
在这项研究中，我们调查了母体剥夺对成年大鼠空间学习和记忆、探索和边缘活动的影响，以及它们与伏隔核（NAc）中多巴胺转运体（DAT）和多巴胺 D1、D2、D3 受体（DRD1、DRD2、DRD3）基因表达的相关性。我们进一步研究了 DNA 甲基化是否参与调节 DRD2 基因表达。我们的行为测试结果表明，母体剥夺显著降低了成年大鼠的空间学习和记忆能力、探索能力和边缘活动，而我们的分子分析结果表明，与对照组相比，母体剥夺大鼠中 DAT、DRD1、DRD2 和 DRD3 的 mRNA 水平显著下调。在母体剥夺大鼠中进行的相关性分析表明，下调的 DAT 和 DRD2 mRNA 水平与找到平台所需的时间显著相关，但只有 DRD2 与 Morris 水迷宫测试中目标象限的时间显著相关；DAT、DRD1 和 DRD2 mRNA 水平与垂直活动次数显著相关，但只有 DRD2 mRNA 水平与旷场测试中的总距离显著相关。相反，DRD3 mRNA 水平与行为变化没有任何相关性。与对照组相比，DRD2 基因启动子区域的甲基化 CpG 水平和 DNA 甲基转移酶 1（Dnmt1）和 3alpha（Dnmt3alpha）的表达在母体剥夺组中没有显著变化。我们得出结论，NAc 中 DAT、DRD1 和 DRD2 基因表达的下调是对探索行为异常的反应；DAT 和 DRD2 表达的下调是对空间学习异常的反应；DRD2 的下调是对母体剥夺大鼠空间记忆异常的反应；而 DRD3 则在这些行为中没有作用。DNA 甲基化可能不是调节 mRNA 水平的机制。
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