Effect of dimethyl fumarate on the changes in the medial prefrontal cortex structure and behavior in the poly(I:C)-induced maternal immune activation model of schizophrenia in the male mice,Behavioural Brain Research

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Effect of dimethyl fumarate on the changes in the medial prefrontal cortex structure and behavior in the poly(I:C)-induced maternal immune activation model of schizophrenia in the male mice
Behavioural Brain Research ( IF 2.6 ) Pub Date : 2021-09-14 , DOI: 10.1016/j.bbr.2021.113581
Farshid Bagheri ₁ , Anahid Safari ₂ , Mohammad Reza Namavar ₃

Affiliation

The link between maternal immune activation (MIA) and the risk of developing schizophrenia (SCZ) later in life has been of major focus in recent years. This link could be bridged by activated inflammatory pathways and excessive cytokine release resulting in adverse effects on behavior, histology, and cytoarchitecture. The down-regulatory effects of immunomodulatory agents on the activated glial cells and their therapeutic effects on schizophrenic patients are consistent with this hypothesis. We investigated whether treatment with the anti-inflammatory drug dimethyl fumarate (DMF) could rescue impacts of prenatal exposure to polyinosinic:polycytidylic acid [poly (I:C)]. Pregnant dams were administered poly(I:C) at gestational day 9.5. Offspring born from these mothers were treated with DMF for fourteen consecutive days from postnatal day 80 and were assessed behaviorally before and after treatment. The brains were then stained with Cresyl Violet or Golgi-Cox. In addition to the estimation of stereological parameters, cytoarchitectural changes were also evaluated in the medial prefrontal cortex. MIA caused some abnormalities in behavior, as well as changes in the number of neurons and non-neurons. These alterations were also extended to pyramidal layer III neurons with a significant decrease in dendritic complexity and spine density which DMF treatment could prevent these changes. Furthermore, DMF treatment was also effective against abnormal exploratory and depression-related behavior, but not the changes in the number of cells. These findings support the idea of using anti-inflammatory agents as adjunctive therapy in patients with SCZ.

中文翻译：

富马酸二甲酯对聚(I:C)诱导的精神分裂症母体免疫激活模型内侧前额叶皮层结构和行为变化的影响

近年来，母体免疫激活（MIA）与晚年患精神分裂症（SCZ）的风险之间的联系一直是人们关注的焦点。这种联系可以通过激活的炎症途径和过度的细胞因子释放来桥接，从而对行为、组织学和细胞结构产生不利影响。免疫调节剂对活化的胶质细胞的下调作用及其对精神分裂症患者的治疗作用与这一假设一致。我们研究了抗炎药物富马酸二甲酯 (DMF) 治疗是否可以挽救产前暴露于聚肌苷:聚胞苷酸 [聚 (I:C)] 的影响。怀孕母鼠在妊娠第 9.5 天时接受聚 (I:C) 注射。这些母亲所生的后代从出生后第 80 天起连续十四天接受 DMF 治疗，并在治疗前后进行行为评估。然后用甲酚紫或高尔基考克斯对大脑进行染色。除了体视学参数的估计之外，还评估了内侧前额叶皮层的细胞结构变化。 MIA 导致一些行为异常，以及神经元和非神经元数量的变化。这些改变也扩展到锥体第三层神经元，树突复杂性和树突棘密度显着降低，DMF 治疗可以防止这些变化。此外，DMF治疗对异常探索和抑郁相关行为也有效，但对细胞数量的变化无效。这些发现支持使用抗炎药作为 SCZ 患者辅助治疗的想法。

更新日期：2021-09-14

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