The Children's Hospital, School of Medicine, Zhejiang University, Hangzhou 310052, China.
The Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310029, China.
Hum Mol Genet. 2020 Sep 29;29(16):2775-2787. doi: 10.1093/hmg/ddaa171.
Adult neurogenesis is regulated by diverse factors including the local environment, i.e. the neurogenic niche. However, whether the lipid in the brain regulates adult neurogenesis and related mechanisms remains largely unknown. In the present study, we found that lipid accumulates in the brain during postnatal neuronal development. Conditional knockout of Fto (cKO) in lipid not only reduced the level of lipid in the brain but also impaired the learning and memory of mice. In addition, Fto deficiency in lipid did not affect the proliferation of adult neural stem cells (aNSCs), but it did inhibit adult neurogenesis by inducing cell apoptosis. Mechanistically, specific deleting Fto in lipid altered gene expression and increased adenosine secretion of adipocytes. The treatment of adenosine promoted the apoptosis of newborn neurons. As a whole, these results reveal the important function of the lipid niche and its associated mechanism in regulating adult neurogenesis.
成人神经发生受多种因素调控，包括局部环境，即神经发生龛。然而，大脑中的脂质是否调节成人神经发生及其相关机制在很大程度上尚不清楚。在本研究中，我们发现脂质在出生后神经元发育过程中在大脑中积累。脂质中 Fto 的条件性敲除（cKO）不仅降低了大脑中的脂质水平，而且损害了小鼠的学习和记忆能力。此外，脂质中的 Fto 缺乏并不影响成年神经干细胞（aNSCs）的增殖，但通过诱导细胞凋亡抑制了成年神经发生。从机制上讲，脂质中特异性敲除 Fto 改变了脂肪细胞的基因表达并增加了腺苷的分泌。腺苷的处理促进了新生神经元的凋亡。总的来说，这些结果揭示了脂质龛及其相关机制在调节成人神经发生中的重要功能。
