Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461.
Department of Genetics, Albert Einstein College of Medicine, Bronx, New York 10461.
J Neurosci. 2021 Mar 31;41(13):2899-2910. doi: 10.1523/JNEUROSCI.2286-20.2021. Epub 2021 Feb 26.
The addition of new neurons to existing neural circuits in the adult brain remains of great interest to neurobiology because of its therapeutic implications. The premier model for studying this process has been the hippocampal dentate gyrus in mice, where new neurons are added to mature circuits during adulthood. Notably, external factors such as an enriched environment (EE) and exercise markedly increase hippocampal neurogenesis. Here, we demonstrate that EE acts by increasing fibroblast growth factor receptor (FGFR) function autonomously within neurogenic cells to expand their numbers in adult male and female mice. FGFRs activated by EE signal through their mediators, FGFR substrate (FRS), to induce stem cell proliferation, and through FRS and phospholipase Cγ to increase the number of adult-born neurons, providing a mechanism for how EE promotes adult neurogenesis. How the environment we live in affects cognition remains poorly understood. In the current study, we explore the mechanism underlying the effects of an enriched environment on the production of new neurons in the adult hippocampal dentate gyrus, a brain area integral in forming new memories. A mechanism is provided for how neural precursor cells in the adult mammalian dentate gyrus respond to an enriched environment to increase their neurogenic output. Namely, an enriched environment acts on stem and progenitor cells by activating fibroblast growth factor receptor signaling through phospholipase Cγ and FGF receptor substrate proteins to expand the pool of precursor cells.
成年大脑中新神经元的加入对于神经生物学来说仍然非常有趣，因为它具有治疗意义。研究这一过程的主要模型是小鼠海马齿状回，成年期新神经元会被添加到成熟的回路中。值得注意的是，外部因素，如丰富的环境（EE）和运动，显著增加了海马神经发生。在这里，我们证明 EE 通过在神经发生细胞内自主增加成纤维细胞生长因子受体（FGFR）的功能来增加成年雄性和雌性小鼠中其数量。EE 激活的 FGFR 通过其介质 FGFR 底物（FRS）传递信号，诱导干细胞增殖，并通过 FRS 和磷脂酶 Cγ 增加成年新生神经元的数量，为 EE 如何促进成年神经发生提供了一种机制。我们生活的环境如何影响认知仍然知之甚少。在目前的研究中，我们探索了丰富环境对成年海马齿状回中新神经元产生的影响的机制，海马齿状回是形成新记忆的重要脑区。为成年哺乳动物齿状回中的神经前体细胞如何对丰富环境做出反应以增加其神经发生输出提供了一种机制。具体来说，丰富的环境通过激活成纤维细胞生长因子受体信号通过磷脂酶 Cγ 和 FGF 受体底物蛋白作用于干细胞和祖细胞，从而扩大前体细胞库。
