Institute for Pharmacology and Toxicology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
Institute of Physiology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
Transl Psychiatry. 2021 Apr 22;11(1):233. doi: 10.1038/s41398-021-01365-z.
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.
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。精神分裂症与大脑和血液中的 BDNF 水平降低有关，但对于 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 在精神分裂症不同小鼠行为表型中的作用。此外，我们评估了丰富环境是否可以预防观察到的变化。在这项研究中，雄性成熟成年野生型和 BDNF 小鼠在认知灵活性（注意力设定转移）、感觉运动门控（前脉冲抑制）和联想情绪学习（安全性和恐惧条件反射）的小鼠范式中进行了测试。在这些测试之前，一半的小鼠暴露于富含环境 2 个月，包括运行轮。测试后，定量了 BDNF 大脑水平。BDNF 小鼠在注意力设定转换任务中普遍存在缺陷，惊跳幅度增加，前脉冲抑制缺陷。上下文恐惧学习不受影响，但安全学习不存在。丰富的环境住房完全预防了 BDNF 小鼠观察到的行为缺陷。值得注意的是，小鼠的行为表现与 BDNF 蛋白水平呈负相关。这些新发现强烈表明，BDNF 水平降低与精神分裂症的几种行为表型有关。此外，丰富的环境会增加 BDNF 蛋白至野生型水平，从而能够挽救这些行为表型。
