Altered dopamine signaling in naturally occurring maternal neglect.
Altered dopamine signaling in naturally occurring maternal neglect.
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自然发生的母亲忽视中多巴胺信号的改变。
DOI：
10.1371/journal.pone.0001974
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发表时间：
2008-04-09
期刊：
影响因子：
3.7
通讯作者：
Stevenson, Sharon A.
中科院分区：
文献类型：
--
作者：
Gammie, Stephen C.;Edelmann, Michelle N.;Mandel-Brehm, Caleigh;D'Anna, Kimberly L.;Auger, Anthony P.;Stevenson, Sharon A.
忽视儿童是虐待儿童最常见的形式，但对母亲忽视的生物学基础了解甚少，也缺乏啮齿动物模型。目前的研究描述了一群小鼠（MaD 1），它们自然表现出母亲忽视（很少或根本不关心后代），平均每代17%。我们确定了一组可以预测未来忽视后代的风险因素，包括自我梳理减少和活动增加。在忽视的时候，忽视的母亲在强迫游泳测试中比养育的母亲游得更多。由疏忽的母亲抚养的交叉寄养后代反过来表现出母亲忽视的风险因素表达增加，成年后母亲照顾减少，暗示可能的表观遗传贡献忽视。出乎意料的是，疏忽母亲的后代引起了母亲的忽视，从交叉培养的养育母亲，这表明调节忽视的因素并不只是在母亲。为了确定母亲忽视的神经通路，我们检查了忽视和养育小鼠的大脑活动。c-Fos的表达显着升高，忽视相对于养育母亲在中枢神经系统，特别是在多巴胺相关的领域，如齿状回（ZI），腹侧被盖区（VTA），和延髓核。磷酸化酪氨酸羟化酶（多巴胺产生的标志物）显着升高，在ZI和更高的VTA（虽然不显着）在疏忽的小鼠。酪氨酸羟化酶水平不变，表明多巴胺活性失调，而不是细胞数量。DARPP-32的磷酸化，多巴胺D1样受体激活的标志物，在疏忽与养育母鼠的中脑核和尾壳核内升高。这些发现表明，母体大脑中的非典型多巴胺活动，特别是在涉及奖励的区域内，参与自然发生的忽视，MaD 1小鼠是了解自然发生的忽视的基础的有用模型。
Child neglect is the most common form of child maltreatment, yet the biological basis of maternal neglect is poorly understood and a rodent model is lacking. The current study characterizes a population of mice (MaD1) which naturally exhibit maternal neglect (little or no care of offspring) at an average rate of 17% per generation. We identified a set of risk factors that can predict future neglect of offspring, including decreased self-grooming and elevated activity. At the time of neglect, neglectful mothers swam significantly more in a forced swim test relative to nurturing mothers. Cross-fostered offspring raised by neglectful mothers in turn exhibit increased expression of risk factors for maternal neglect and decreased maternal care as adults, suggestive of possible epigenetic contributions to neglect. Unexpectedly, offspring from neglectful mothers elicited maternal neglect from cross-fostered nurturing mothers, suggesting that factors regulating neglect are not solely within the mother. To identify a neurological pathway underlying maternal neglect, we examined brain activity in neglectful and nurturing mice. c-Fos expression was significantly elevated in neglectful relative to nurturing mothers in the CNS, particularly within dopamine associated areas, such as the zona incerta (ZI), ventral tegmental area (VTA), and nucleus accumbens. Phosphorylated tyrosine hydroxylase (a marker for dopamine production) was significantly elevated in ZI and higher in VTA (although not significantly) in neglectful mice. Tyrosine hydroxylase levels were unaltered, suggesting a dysregulation of dopamine activity rather than cell number. Phosphorylation of DARPP-32, a marker for dopamine D1-like receptor activation, was elevated within nucleus accumbens and caudate-putamen in neglectful versus nurturing dams. These findings suggest that atypical dopamine activity within the maternal brain, especially within regions involved in reward, is involved in naturally occurring neglect and that MaD1 mice are a useful model for understanding the basis of naturally occurring neglect.
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