Juvenile antioxidant treatment prevents adult deficits in a developmental model of schizophrenia.

Juvenile antioxidant treatment prevents adult deficits in a developmental model of schizophrenia.
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DOI:
10.1016/j.neuron.2014.07.028
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发表时间:
2014-09-03
期刊:
影响因子:
16.2
通讯作者:
O'Donnell P
O'Donnell P
中科院分区:
医学1区
文献类型:
--
作者:
Cabungcal JH;Counotte DS;Lewis E;Tejeda HA;Piantadosi P;Pollock C;Calhoon GG;Sullivan E;Presgraves E;Kil J;Hong LE;Cuenod M;Do KQ;O'Donnell P

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发育异常可能导致成年人大脑功能的缺陷,这可能是精神分裂症等精神疾病的潜在轨迹。在啮齿类动物中产生成年缺陷的发育操作提供了一个机会,以探索发育改变驱动的异常延迟出现的机制。在这里,我们评估是否氧化应激在症状前阶段导致成年异常的新生儿腹侧海马病变,发育啮齿动物模型精神分裂症的研究有用的大鼠。青少年和青少年治疗与抗氧化剂N-乙酰半胱氨酸防止减少前额叶小白蛋白interneuron的活动在这个模型中观察到的,以及与精神分裂症相关的电生理和行为缺陷。用谷胱甘肽过氧化物酶模拟物依布硒啉治疗青少年也逆转了这种动物模型的行为缺陷。这些研究结果表明,症状前氧化应激产生异常的成人脑功能发育受损的大脑,并强调氧化还原调节作为早期干预的潜在目标。
Abnormal development can lead to deficits in adult brain function, a trajectory likely underlying adolescent-onset psychiatric conditions such as schizophrenia. Developmental manipulations yielding adult deficits in rodents provide an opportunity to explore mechanisms involved in a delayed emergence of anomalies driven by developmental alterations. Here we assessed whether oxidative stress during presymptomatic stages causes adult anomalies in rats with a neonatal ventral hippocampal lesion, a developmental rodent model useful for schizophrenia research. Juvenile and adolescent treatment with the antioxidant N-acetyl cysteine prevented the reduction of prefrontal parvalbumin interneuron activity observed in this model, as well as electrophysiological and behavioral deficits relevant to schizophrenia. Adolescent treatment with the glutathione peroxidase mimic ebselen also reversed behavioral deficits in this animal model. These findings suggest that presymptomatic oxidative stress yields abnormal adult brain function in a developmentally compromised brain, and highlight redox modulation as a potential target for early intervention.
精神分裂症的皮质性白蛋白中间神经元和认知功能障碍。
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