Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA; Psychological Science Department, Vassar College, 124 Raymond Avenue, Poughkeepsie, NY 12604, USA.
Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.
Curr Biol. 2017 Dec 18;27(24):3859-3863.e3. doi: 10.1016/j.cub.2017.10.071. Epub 2017 Nov 30.
Tumor necrosis factor alpha (TNF-α) is a cytokine that not only coordinates local and systemic immune responses [1, 2] but also regulates neuronal functions. Most prominently, glia-derived TNF-α has been shown to regulate homeostatic synaptic scaling [3-6], but TNF-α-null mice exhibited no apparent cognitive or emotional abnormalities. Instead, we found a TNF-α-dependent intergenerational effect, as mothers with a deficit in TNF-α programmed their offspring to exhibit low innate fear. Cross-fostering and conditional knockout experiments indicated that a TNF-α deficit in the maternal brain, rather than in the hematopoietic system, and during gestation was responsible for the low-fear offspring phenotype. The level of innate fear governs the balance between exploration/foraging and avoidance of predators and is thus fundamentally important in adaptation, fitness, and survival [7]. Because maternal exercise and activity are known to reduce both brain TNF-α [8] and offspring innate fear [9], whereas maternal stress has been reported to increase brain TNF-α [10] and offspring fear and anxiety [11, 12], maternal brain TNF-α may report environmental conditions to promote offspring behavioral adaptation to their anticipated postnatal environment.
肿瘤坏死因子-α（TNF-α）是一种细胞因子，它不仅协调局部和全身免疫反应[1,2]，还调节神经元功能。[3-6]最突出的是，胶质细胞衍生的 TNF-α 已被证明调节稳态突触缩放，但 TNF-α 基因敲除小鼠没有表现出明显的认知或情绪异常。相反，我们发现了 TNF-α 依赖的代际效应，因为 TNF-α 缺乏的母亲使她们的后代表现出低先天恐惧。交叉寄养和条件性基因敲除实验表明，母脑中的 TNF-α 缺乏，而不是造血系统中的 TNF-α 缺乏，以及在妊娠期，是导致低恐惧后代表型的原因。先天恐惧的水平控制着探索/觅食和避免捕食者之间的平衡，因此在适应、适应能力和生存方面具有根本重要性[7]。因为众所周知，母体运动和活动会降低大脑中的 TNF-α[8]和后代的先天恐惧[9]，而母体压力被报道会增加大脑中的 TNF-α[10]和后代的恐惧和焦虑[11,12]，因此，母脑 TNF-α 可能会报告环境条件，以促进后代行为适应其预期的产后环境。
