BDNF haploinsufficiency induces behavioral endophenotypes of schizophrenia in male mice that are rescued by enriched environment.
BDNF haploinsufficiency induces behavioral endophenotypes of schizophrenia in male mice that are rescued by enriched environment.
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DOI：
10.1038/s41398-021-01365-z
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发表时间：
2021-04-22
影响因子：
6.8
通讯作者：
Fendt M
中科院分区：
文献类型：
--
作者：
Harb M;Jagusch J;Durairaja A;Endres T;Leßmann V;Fendt M
脑源性神经营养因子（BDNF）参与了许多对大脑健康功能至关重要的过程。精神分裂症与脑和血液中BDNF水平低有关，然而，关于BDNF在精神分裂症不同症状中的作用知之甚少。在这里，我们使用BDNF-单倍不足（BDNF+/−）小鼠来研究BDNF在精神分裂症的不同小鼠行为内表型中的作用。此外，我们评估了丰富的环境是否可以防止观察到的变化。在这项研究中，在小鼠模型中测试了雄性成熟成年野生型和脑源性神经营养因子+/-小鼠的认知灵活性（注意力集中转移）、感觉运动门控（前脉冲抑制）和联想情绪学习（安全和恐惧条件反射）。在这些测试之前，一半的小鼠暴露在丰富的环境中2个月，包括跑步轮。测试后，定量BDNF脑水平。BDNF+/−小鼠在注意力转移任务中存在普遍缺陷，惊吓幅度增加，前脉冲抑制缺陷。情境恐惧学习没有受到影响，但安全学习缺席。丰富的环境完全防止了BDNF+/−小鼠中观察到的行为缺陷。值得注意的是，小鼠的行为表现与BDNF蛋白水平呈负相关。这些新的发现有力地表明，BDNF水平下降与精神分裂症的几种行为内表型有关。此外，丰富的环境增加BDNF蛋白到野生型水平，从而能够拯救这些行为内表型。
Brain-derived neurotrophic factor (BDNF) is implicated in a number of processes that are crucial for healthy functioning of the brain. Schizophrenia is associated with low BDNF levels in the brain and blood, however, not much is known about BDNF’s role in the different symptoms of schizophrenia. Here, we used BDNF-haploinsufficient (BDNF+/−) mice to investigate the role of BDNF in different mouse behavioral endophenotypes of schizophrenia. Furthermore, we assessed if an enriched environment can prevent the observed changes. In this study, male mature adult wild-type and BDNF+/− mice were tested in mouse paradigms for cognitive flexibility (attentional set shifting), sensorimotor gating (prepulse inhibition), and associative emotional learning (safety and fear conditioning). Before these tests, half of the mice had a 2-month exposure to an enriched environment, including running wheels. After the tests, BDNF brain levels were quantified. BDNF+/− mice had general deficits in the attentional set-shifting task, increased startle magnitudes, and prepulse inhibition deficits. Contextual fear learning was not affected but safety learning was absent. Enriched environment housing completely prevented the observed behavioral deficits in BDNF+/− mice. Notably, the behavioral performance of the mice was negatively correlated with BDNF protein levels. These novel findings strongly suggest that decreased BDNF levels are associated with several behavioral endophenotypes of schizophrenia. Furthermore, an enriched environment increases BDNF protein to wild-type levels and is thereby able to rescue these behavioral endophenotypes.
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影响因子：
3.7
作者：
Castello NA;Nguyen MH;Tran JD;Cheng D;Green KN;LaFerla FM
通讯作者：
LaFerla FM
影响因子：
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作者：
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Pearlson, Godfrey D.
影响因子：
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作者：
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通讯作者：
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影响因子：
1.7
作者：
Coppola, V;Tessarollo, L
通讯作者：
Tessarollo, L
DOI：
10.1016/j.molbrainres.2003.11.002
发表时间：
2004-02-05
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Chourbaji, S;Hellweg, R;Gass, P
通讯作者：
Gass, P