The notion that schizophrenia is a neurodevelopmental disorder in which neuropathologies evolve gradually over the developmental course indicates a potential therapeutic window during which pathophysiological processes may be modified to halt disease progression or reduce its severity. Here we used a neurodevelopmental maternal immune stimulation (MIS) rat model of schizophrenia to test whether early targeted modulatory intervention would affect schizophrenia's neurodevelopmental course. We applied deep brain stimulation (DBS) or sham stimulation to the medial prefrontal cortex (mPFC) of adolescent MIS rats and respective controls, and investigated its behavioral, biochemical, brain-structural and -metabolic effects in adulthood. We found that mPFC-DBS successfully prevented the emergence of deficits in sensorimotor gating, attentional selectivity and executive function in adulthood, as well as the enlargement of lateral ventricle volumes and mal-development of dopaminergic and serotonergic transmission. These data suggest that the mPFC may be a valuable target for effective preventive treatments. This may have significant translational value, suggesting that targeting the mPFC before the onset of psychosis via less invasive neuromodulation approaches may be a viable preventive strategy.

中文翻译：

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在精神分裂症的啮齿动物模型中，早期的神经调节可防止脑部发育和行为异常。

精神分裂症是一种神经发育障碍，其中神经病理学在整个发展过程中逐渐发展，这一观点表明了潜在的治疗窗口，在此期间，可以修改病理生理过程以阻止疾病进展或降低其严重程度。在这里，我们使用精神分裂症的神经发育母体免疫刺激（MIS）大鼠模型来测试早期的定向调节干预是否会影响精神分裂症的神经发育过程。我们将深部脑刺激（DBS）或假刺激应用于青春期MIS大鼠和相应对照组的内侧前额叶皮层（mPFC），并研究其在成年期的行为，生化，脑结构和代谢作用。我们发现mPFC-DBS成功地阻止了感觉运动门控的缺陷的出现，在成年期的注意力选择性和执行功能，以及侧脑室容积的扩大和多巴胺能和血清素能传递的不良发展。这些数据表明，mPFC可能是有效预防治疗的重要目标。这可能具有重要的翻译价值，表明在精神病发作之前通过侵入性较小的神经调节方法靶向mPFC可能是可行的预防策略。