Adolescent stress leads to glutamatergic disturbance through dopaminergic abnormalities in the prefrontal cortex of genetically vulnerable mice.
Adolescent stress leads to glutamatergic disturbance through dopaminergic abnormalities in the prefrontal cortex of genetically vulnerable mice.
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DOI：
10.1007/s00213-017-4704-8
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发表时间：
2017-10
影响因子：
3.4
通讯作者：
Nabeshima T
中科院分区：
文献类型：
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作者：
Matsumoto Y;Niwa M;Mouri A;Noda Y;Fukushima T;Ozaki N;Nabeshima T
青少年时期的压力会影响产后成熟和成年后的行为模式。青春期应激诱导的神经元分子和功能变化是精神疾病（包括精神分裂症）的关键临床特征。在本研究中，我们暴露在遗传上脆弱的小鼠隔离压力，以检查在多巴胺能神经系统的分子变化，涉及N-甲基-D-天冬氨酸（NMDA）受体通过多巴胺能障碍在前额叶皮层（PFc）。我们报告说，青春期后期的压力与分裂症1（DISC 1）遗传风险相结合，引起PFc中谷氨酸能神经元的改变，如谷氨酸转运蛋白表达增加，细胞外谷氨酸水平降低，d-丝氨酸浓度降低，NMDA-Ca 2 +/钙调蛋白激酶II信号转导的激活受损。这些变化导致在自发活动，强迫游泳，社会交往，和新奇偏好测试的行为缺陷。如果动物用非典型抗精神病药物氯氮平和多巴胺D1激动剂SKF 81297治疗，则可以防止PFc中的多巴胺能改变，这表明多巴胺能神经元的激活参与了多巴胺能系统的调节。我们的研究结果表明，青春期的压力结合多巴胺能异常的遗传易感小鼠的PFc诱导的mammatergic干扰，这导致在年轻的成年阶段的行为缺陷。
Stress during the adolescent period influences postnatal maturation and behavioral patterns in adulthood. Adolescent stress-induced molecular and functional changes in neurons are the key clinical features of psychiatric disorders including schizophrenia. In the present study, we exposed genetically vulnerable mice to isolation stress to examine the molecular changes in the glutamatergic system involving N-methyl-d-aspartate (NMDA) receptors via dopaminergic disturbance in the prefrontal cortex (PFc). We report that late adolescent stress in combination with Disrupted-in-Schizophrenia 1 (DISC1) genetic risk elicited alterations in glutamatergic neurons in the PFc, such as increased expression of glutamate transporters, decreased extracellular levels of glutamate, decreased concentration of d-serine, and impaired activation of NMDA-Ca2+/calmodulin kinase II signaling. These changes resulted in behavioral deficits in locomotor activity, forced swim, social interaction, and novelty preference tests. The glutamatergic alterations in the PFc were prevented if the animals were treated with an atypical antipsychotic drug clozapine and a dopamine D1 agonist SKF81297, which suggests that the activation of dopaminergic neurons is involved in the regulation of the glutamatergic system. Our results suggest that adolescent stress combined with dopaminergic abnormalities in the PFc of genetically vulnerable mice induces glutamatergic disturbances, which leads to behavioral deficits in the young adult stage.
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影响因子：
11
作者：
Furukubo-Tokunaga K;Kurita K;Honjo K;Pandey H;Ando T;Takayama K;Arai Y;Mochizuki H;Ando M;Kamiya A;Sawa A
通讯作者：
Sawa A
影响因子：
1.8
作者：
Fukushima, T;Kawai, J;Toyo'oka, T
通讯作者：
Toyo'oka, T
影响因子：
3.7
作者：
Fukushima T;Iizuka H;Yokota A;Suzuki T;Ohno C;Kono Y;Nishikiori M;Seki A;Ichiba H;Watanabe Y;Hongo S;Utsunomiya M;Nakatani M;Sadamoto K;Yoshio T
通讯作者：
Yoshio T
DOI：
10.1017/s146114571000009x
发表时间：
2010-11
期刊：
The international journal of neuropsychopharmacology
影响因子：
--
作者：
Bortolozzi A;Masana M;Díaz-Mataix L;Cortés R;Scorza MC;Gingrich JA;Toth M;Artigas F
通讯作者：
Artigas F
影响因子：
11
作者：
通讯作者：
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