Glutathione Deficiency during Early Postnatal Development Causes Schizophrenia-Like Symptoms and a Reduction in BDNF Levels in the Cortex and Hippocampus of Adult Sprague-Dawley Rats.
Glutathione Deficiency during Early Postnatal Development Causes Schizophrenia-Like Symptoms and a Reduction in BDNF Levels in the Cortex and Hippocampus of Adult Sprague-Dawley Rats.
复制标题
DOI：
10.3390/ijms22126171
复制
发表时间：
2021-06-08
影响因子：
5.6
通讯作者：
Lorenc-Koci E
中科院分区：
文献类型：
--
作者：
Lech MA;Leśkiewicz M;Kamińska K;Rogóż Z;Lorenc-Koci E
越来越多的证据表明，脑中氧化还原状态的失调是精神分裂症发病机制的重要因素。本研究的目的是评价谷胱甘肽（GSH）合成抑制剂1-丁硫基-（S，R）-亚砜亚胺（BSO）和1-[2-Bis]（4-氟苯基）甲氧基]乙基]-4-（4-氟苯基）甲氧基（3-苯丙基）哌嗪二盐酸盐（GBR 12909），一种多巴胺再摄取抑制剂，单独或联合给药于出生后早期发育（p5-p16）的Sprague-Dawley幼仔，对精神分裂症样行为发生的时间进程以及成年期前额叶皮层（PFC）和海马（HIP）脑源性神经营养因子（BDNF）mRNA及其蛋白表达的影响。BSO单独给药降低PFC和HIP中BDNF mRNA及其蛋白的水平。BSO + GBR 12909联合处理也降低PFC中BDNF mRNA及其蛋白的水平，但在HIP中，仅降低BDNF蛋白的水平。在青春期（p30，p42-p44，p60-p62）和成年早期（p90-p92）的三个时间点，使用社会互动测试，新物体识别测试和旷场测试评估大鼠的精神分裂症样行为。社交和认知缺陷首先出现在青春期中期，并持续发生到成年期，无论是在BSO单独给药还是BSO + GBR 12909联合给药的大鼠中。人类阳性症状对应的行为发生在青春期中期，仅在BSO + GBR 12909处理的大鼠中发生。只有在后一组中，安非他明加重了成年后现有的阳性症状。我们的数据显示，在出生后早期接受BSO + GBR 12909组合的大鼠几乎再现了在精神分裂症患者中观察到的所有症状，因此，可以被认为是这种疾病的有价值的神经发育模型。
Growing body of evidence points to dysregulation of redox status in the brain as an important factor in the pathogenesis of schizophrenia. The aim of our study was to evaluate the effects of l-buthionine-(S,R)-sulfoximine (BSO), a glutathione (GSH) synthesis inhibitor, and 1-[2-Bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride (GBR 12909), a dopamine reuptake inhibitor, given alone or in combination, to Sprague–Dawley pups during early postnatal development (p5–p16), on the time course of the onset of schizophrenia-like behaviors, and on the expression of brain-derived neurotrophic factor (BDNF) mRNA and its protein in the prefrontal cortex (PFC) and hippocampus (HIP) during adulthood. BSO administered alone decreased the levels of BDNF mRNA and its protein both in the PFC and HIP. Treatment with the combination of BSO + GBR 12909 also decreased BDNF mRNA and its protein in the PFC, but in the HIP, only the level of BDNF protein was decreased. Schizophrenia-like behaviors in rats were assessed at three time points of adolescence (p30, p42–p44, p60–p62) and in early adulthood (p90–p92) using the social interaction test, novel object recognition test, and open field test. Social and cognitive deficits first appeared in the middle adolescence stage and continued to occur into adulthood, both in rats treated with BSO alone or with the BSO + GBR 12909 combination. Behavior corresponding to positive symptoms in humans occurred in the middle adolescence period, only in rats treated with BSO + GBR 12909. Only in the latter group, amphetamine exacerbated the existing positive symptoms in adulthood. Our data show that rats receiving the BSO + GBR 12909 combination in the early postnatal life reproduced virtually all symptoms observed in patients with schizophrenia and, therefore, can be considered a valuable neurodevelopmental model of this disease.
登录
查看更多内容
影响因子：
2.9
作者：
Ashe, PC;Chlan-Fourney, J;Li, XM
通讯作者：
Li, XM
DOI：
10.1017/s1461145704004110
发表时间：
2004-03-01
影响因子：
4.8
作者：
Abi-Dargham, A
通讯作者：
Abi-Dargham, A
影响因子：
8.2
作者：
Bitanihirwe, Byron K. Y.;Woo, Tsung-Ung W.
通讯作者：
Woo, Tsung-Ung W.
DOI：
10.1017/s1461145710000805
发表时间：
2011-02-01
影响因子：
4.8
作者：
Gawryluk, Jeremy W.;Wang, Jun-Feng;Young, L. Trevor
通讯作者：
Young, L. Trevor
影响因子：
--
作者：
Danion, JM;Rizzo, L;Bruant, A
通讯作者：
Bruant, A