Deep brain stimulation improves behavior and modulates neural circuits in a rodent model of schizophrenia
Deep brain stimulation improves behavior and modulates neural circuits in a rodent model of schizophrenia
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DOI：
10.1016/j.expneurol.2016.06.012
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发表时间：
2016-09-01
影响因子：
5.3
通讯作者：
Hamani, Clement
中科院分区：
文献类型：
--
作者：
Bikovsky, Lior;Hadar, Ravit;Hamani, Clement
精神分裂症是一种使人衰弱的精神疾病，大量患者对治疗没有充分反应。脑深部电刺激（DBS）是一种目前正在研究的用于治疗难治性精神疾病的手术技术。在这里，我们使用聚I：C大鼠精神分裂症模型，研究内侧前额叶皮层（mPFC）和Nacc（Nacc）DBS对两个行为精神分裂症样缺陷，即感觉运动门控，如前脉冲抑制（PPI）中断所反映的，和注意选择性，如潜伏抑制（LI）中断所反映的影响。此外，使用FDG PET研究了DBS对神经回路的影响。我们发现，mPFC-和Nacc-DBS缓解PPI和LI异常聚I：C后代，而Nacc-但不是mPFC-DBS破坏PPI和LI在盐水后代。在盐水后代中，mPFC-DBS增加了顶叶皮质、纹状体、腹侧海马和Nacc的代谢，同时减少了脑干、小脑、下丘脑和导水管周围灰质的代谢。另一方面，Nacc-DBS增加了腹侧海马和嗅球的活动，减少了隔区、脑干、导水管周围灰质和下丘脑的活动。在聚I：C后代代谢的变化后mPFC-DBS的生理盐水后代中记录的相似，除了在脑干和下丘脑的活动减少。相比之下，Nacc-DBS未诱导聚I：C后代的脑代谢发生任何统计学变化。我们的研究表明，mPFC-或Nacc-DBS交付给聚I：C处理的母鼠的成年后代改善PPI和LI的缺陷。尽管有共同的行为反应，但两个靶点的刺激诱导了不同的代谢效应。(C)2016由Elsevier Inc.出版
Schizophrenia is a debilitating psychiatric disorder with a significant number of patients not adequately responding to treatment. Deep brain stimulation (DBS) is a surgical technique currently investigated for medically-refractory psychiatric disorders. Here, we use the poly I:C rat model of schizophrenia to study the effects of medial prefrontal cortex (mPFC) and nucleus accumbens (Nacc) DBS on two behavioral schizophrenia-like deficits, i.e. sensorimotor gating, as reflected by disrupted prepulse inhibition (PPI), and attentional selectivity, as reflected by disrupted latent inhibition (LI). In addition, the neurocircuitry influenced by DBS was studied using FDG PET. We found that mPFC- and Nacc-DBS alleviated PPI and LI abnormalities in poly I:C offspring, whereas Nacc- but not mPFC-DBS disrupted PPI and LI in saline offspring. In saline offspring, mPFC-DBS increased metabolism in the parietal cortex, striatum, ventral hippocampus and Nacc, while reducing it in the brainstem, cerebellum, hypothalamus and periaqueductal gray. Nacc-DBS, on the other hand, increased activity in the ventral hippocampus and olfactory bulb and reduced it in the septal area, brainstem, periaqueductal gray and hypothalamus. In poly I:C offspring changes in metabolism following mPFC-DBS were similar to those recorded in saline offspring, except for a reduced activity in the brainstem and hypothalamus. In contrast, Nacc-DBS did not induce any statistical changes in brain metabolism in poly I:C offspring. Our study shows that mPFC- or Nacc-DBS delivered to the adult progeny of poly I:C treated dams improves deficits in PPI and LI. Despite common behavioral responses, stimulation in the two targets induced different metabolic effects. (C) 2016 Published by Elsevier Inc.