Prenatal Exposure to Antipsychotics Disrupts the Plasticity of Dentate Neurons and Memory in Adult Male Mice.
Prenatal Exposure to Antipsychotics Disrupts the Plasticity of Dentate Neurons and Memory in Adult Male Mice.
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产前接触抗精神病药物会破坏成年雄性小鼠齿状神经元和记忆的可塑性
DOI：
10.1093/ijnp/pyy073
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发表时间：
2019-01-01
期刊：
影响因子：
--
通讯作者：
Su YA
中科院分区：
文献类型：
--
作者：
Wang H;Li JT;Zhang Y;Liu R;Wang XD;Si TM;Su YA
摘要背景随着越来越多地使用第二代抗精神病药物治疗妊娠期精神疾病，人们对这些药物对后代神经发育的长期影响表示担忧。然而，产前抗精神病药物暴露的持久影响的临床前和临床证据仍然稀少。方法将广泛使用的第二代抗精神病药利培酮和第一代抗精神病药氟哌啶醇分别给予孕6 ~ 16 d的C57 BL/6 N小鼠。行为测试，免疫组织化学染色，Golgi-Cox技术，和蛋白质印迹法被用来确定产前抗精神病药物暴露对成年雄性小鼠齿状回的可塑性和相关行为的影响。结果产前氟哌啶醇和利培酮暴露小鼠均表现出认知记忆障碍，但无焦虑相关行为。此外，产前氟哌啶醇和利培酮暴露损害成年出生的齿状颗粒细胞的增殖和成熟。我们发现氟哌啶醇暴露降低树突状颗粒细胞的长度，而利培酮没有影响。然而，这两种药物抑制颗粒细胞中的树突分支。氟哌啶醇暴露也显着降低总棘密度在中间树突状齿状回。出生前暴露于利培酮的小鼠仅表现出齿状回锥体下叶薄棘和蘑菇棘的丢失。总的来说，产前氟哌啶醇暴露比利培酮产生更强烈的负面影响。结论抗精神病药物暴露对海马可塑性和行为的长期编程效应提供了证据。
Abstract Background With the growing use of second-generation antipsychotics for the treatment of a spectrum of psychiatric illnesses in pregnancy, concerns have been raised about the long-term impact of these medications on offspring neurodevelopment. However, preclinical and clinical evidence on the lasting effects of prenatal antipsychotic exposure is still sparse. Methods Risperidone, a widely used second-generation antipsychotic, and haloperidol, a representative first-generation antipsychotic, were administered to pregnant C57BL/6N mice from embryonic day 6 to 16. Behavioral tests, immunohistochemical staining, Golgi-Cox technique, and western blot were used to determine the effects of prenatal antipsychotic exposure on the plasticity of the dentate gyrus and related behavior in adult male mice. Results Both prenatal haloperidol- and risperidone-exposed mice showed recognition memory deficits but had no anxiety-related behavior. In addition, both prenatal haloperidol and risperidone exposure impaired the proliferation and maturation of adult-born dentate granule cells. We found that haloperidol exposure decreased dendritic length of dentate granule cells, while risperidone had no effect. However, both drugs inhibited dendrite branching in granule cells. Haloperidol exposure also significantly reduced total spine density in the middle dendritic segment of dentate gyrus. Prenatally risperidone-exposed mice only displayed a loss in thin and mushroom spines of infrapyramidal blade of dentate gyrus. Collectively, prenatal haloperidol exposure exerted more robust negative effects than risperidone. Conclusion These data provide evidence for the long-term programming effects of early-life exposure to antipsychotics on hippocampal plasticity and behavior.
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DOI：
10.1002/syn.21900
发表时间：
2016-07
期刊：
Synapse (New York, N.Y.)
影响因子：
--
作者：
Gallitano AL;Satvat E;Gil M;Marrone DF
通讯作者：
Marrone DF
影响因子：
16.2
作者：
Fanselow, Michael S.;Dong, Hong-Wei
通讯作者：
Dong, Hong-Wei
影响因子：
3
作者：
GLASER, EM;VANDERLOOS, H
通讯作者：
VANDERLOOS, H
树突状棘的超微结构：突触和脊柱形态之间的相关性。
影响因子：
4.3
作者：
Arellano JI;Benavides-Piccione R;Defelipe J;Yuste R
通讯作者：
Yuste R
影响因子：
24.8
作者：
Leuner B;Gould E
通讯作者：
Gould E