Deep brain stimulation during early adolescence prevents microglial alterations in a model of maternal immune activation
Deep brain stimulation during early adolescence prevents microglial alterations in a model of maternal immune activation
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DOI：
10.1016/j.bbi.2016.12.003
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发表时间：
2017-07-01
影响因子：
15.1
通讯作者：
Winter, Christine
中科院分区：
文献类型：
--
作者：
Hadar, Ravit;Dong, Le;Winter, Christine
近年来，精神分裂症被认为是一种神经发育障碍，可能涉及围产期损伤，逐渐影响大脑发育。聚I：C母体免疫激活（MIA）啮齿动物模型被认为是精神分裂症的神经发育模型。使用这个模型，我们和其他人证明了改变的小胶质细胞形式的神经炎症与精神分裂症样内表型之间的关联。使用抗炎药物米诺环素的治疗干预影响了改变的小胶质细胞激活，并在成年后代中取得了成功。然而，很少有人知道预防性治疗策略对小胶质细胞特性的影响。以前，我们发现，脑深部刺激内侧前额叶皮层适用于pre-emptically青春期MIA大鼠防止成年大鼠的行为和结构缺陷的表现。我们在这里研究了青春期脑深部电刺激对成年期小胶质细胞特性的影响。我们发现在MIA大鼠的海马和丘脑核，而不是在内侧前额叶皮质，小胶质细胞密度和索马体的大小增加。在植入和刺激之前和之后，促炎细胞因子mRNA在所有脑区中均未发生变化。刺激内侧前额叶皮层或脑桥核使包括海马在内的主要投射区域和电极植入周围区域的小胶质细胞密度和索马大小正常化。我们的结论是，在平行的缓解症状的大鼠MIA模型，脑深部电刺激有可能防止这种疾病的神经炎症成分。(C)2016 Elsevier Inc. All rights reserved.
In recent years schizophrenia has been recognized as a neurodevelopmental disorder likely involving a perinatal insult progressively affecting brain development. The poly I:C maternal immune activation (MIA) rodent model is considered as a neurodevelopmental model of schizophrenia. Using this model we and others demonstrated the association between neuroinflammation in the form of altered microglia and a schizophrenia-like endophenotype. Therapeutic intervention using the anti-inflammatory drug minocycline affected altered microglia activation and was successful in the adult offspring. However, less is known about the effect of preventive therapeutic strategies on microglia properties. Previously we found that deep brain stimulation of the medial prefrontal cortex applied pre-symptomatically to adolescence MIA rats prevented the manifestation of behavioral and structural deficits in adult rats. We here studied the effects of deep brain stimulation during adolescence on microglia properties in adulthood. We found that in the hippocampus and nucleus accumbens, but not in the medial prefrontal cortex, microglial density and soma size were increased in MIA rats. Pro-inflammatory cytokine mRNA was unchanged in all brain areas before and after implantation and stimulation. Stimulation of either the medial prefrontal cortex or the nucleus accumbens normalized microglia density and soma size in main projection areas including the hippocampus and in the area around the electrode implantation. We conclude that in parallel to an alleviation of the symptoms in the rat MIA model, deep brain stimulation has the potential to prevent the neuroinflammatory component in this disease. (C) 2016 Elsevier Inc. All rights reserved.