Maternal immune activation leads to atypical turning asymmetry and reduced DRD2 mRNA expression in a rat model of schizophrenia
Maternal immune activation leads to atypical turning asymmetry and reduced DRD2 mRNA expression in a rat model of schizophrenia
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DOI：
10.1016/j.bbr.2021.113504
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发表时间：
2021-07-31
影响因子：
2.7
通讯作者：
Freund, Nadja
中科院分区：
文献类型：
--
作者：
Mundorf, Annakarina;Kubitza, Nadja;Freund, Nadja
据报道，被诊断为精神分裂症的个体存在非典型的不对称性，这将较高的症状严重程度与较弱的偏侧化联系起来。此外，偏侧化和精神分裂症都受到多巴胺能系统的影响。然而，精神分裂症的病因与非典型不对称之间是否存在直接联系仍有待研究。在这项研究中，我们检查了母体免疫激活（MIA）（一种精神分裂症的发育动物模型，已知会改变多巴胺能系统）是否会诱导青少年和成年后代的非典型偏侧化。由于多巴胺能系统在两者中都发挥着关键作用，因此我们分析了神经元多巴胺 D2 受体 (DRD2) mRNA 表达。在妊娠第 15 天，通过注射 10 mg/kg 聚肌胞苷酸：多胞苷酸 (PolyI:C) 来诱导 MIA。对照组注射 0.9% NaCl。后代在青春期或成年早期在旷场测试中测试转向行为的不对称性。使用 DeepLabCut 评估每只动物的左转和右转总数。通过计算偏侧化商来分析不对称的强度和偏好侧。此外，还使用实时 PCR 分析了两个年龄段后代前额皮质中 DRD2 mRNA 的表达。 MIA 与青少年的右转行为有关。在成人中，MIA 与转动偏差的缺失相关，表明 MIA 后不对称性减少。 DRD2 mRNA 表达分析显示，与对照组相比，MIA 后青少年动物的 mRNA 水平显着降低，但成年动物则不然。我们的结果强化了非典型不对称、DRD2 mRNA 表达减少和精神分裂症之间的关联。然而，还需要更多的临床前研究。
Atypical asymmetries have been reported in individuals diagnosed with schizophrenia, linking higher symptom severity to weaker lateralization. Furthermore, both lateralization and schizophrenia are influenced by the dopaminergic system. However, whether a direct link between the etiology of schizophrenia and atypical asymmetries exists is yet to be investigated. In this study, we examined whether maternal immune activation (MIA), a developmental animal model for schizophrenia and known to alter the dopaminergic system, induces atypical lateralization in adolescent and adult offspring. As the dopaminergic system is a key player in both, we analyzed neuronal dopamine D2 receptor (DRD2) mRNA expression. MIA was induced by injecting pregnant rats with 10 mg/kg polyinosinic:polycytidylic (PolyI:C) at gestational day 15. Controls were injected with 0.9 % NaCl. Offspring were tested at adolescence or early adulthood for asymmetry of turning behavior in the open field test. The total number of left and right turns per animal was assessed using DeepLabCut. Strength and preferred side of asymmetry were analyzed by calculating lateralization quotients. Additionally, DRD2 mRNA expression in the prefrontal cortex of offspring at both ages was analyzed using real-time PCR. MIA was associated with a rightward turning behavior in adolescents. In adults, MIA was associated with an absence of turning bias, indicating reduced asymmetry after MIA. The analysis of DRD2 mRNA expression revealed significantly lower mRNA levels after MIA compared to controls in adolescent, but not adult animals. Our results reinforce the association between atypical asymmetries, reduced DRD2 mRNA expression, and schizophrenia. However, more preclinical research is needed.