Nursing School, University of Campinas, Campinas, Brazil.
Laboratory of Cell Signaling, University of Campinas, Rua Cinco de Junho, 350, Cidade Universitária, Campinas, SP, 13083-877, Brazil.
J Neuroinflammation. 2021 Aug 31;18(1):192. doi: 10.1186/s12974-021-02242-8.
Interleukin-6 (IL6) produced in the context of exercise acts in the hypothalamus reducing obesity-associated inflammation and restoring the control of food intake and energy expenditure. In the hippocampus, some of the beneficial actions of IL6 are attributed to its neurogenesis-inducing properties. However, in the hypothalamus, the putative neurogenic actions of IL6 have never been explored, and its potential to balance energy intake can be an approach to prevent or attenuate obesity.
Wild-type (WT) and IL6 knockout (KO) mice were employed to study the capacity of IL6 to induce neurogenesis. We used cell labeling with Bromodeoxyuridine (BrdU), immunofluorescence, and real-time PCR to determine the expression of markers of neurogenesis and neurotransmitters. We prepared hypothalamic neuroprogenitor cells from KO that were treated with IL6 in order to provide an ex vivo model to further characterizing the neurogenic actions of IL6 through differentiation assays. In addition, we analyzed single-cell RNA sequencing data and determined the expression of IL6 and IL6 receptor in specific cell types of the murine hypothalamus.
IL6 expression in the hypothalamus is low and restricted to microglia and tanycytes, whereas IL6 receptor is expressed in microglia, ependymocytes, endothelial cells, and astrocytes. Exogenous IL6 reduces diet-induced obesity. In outbred mice, obesity-resistance is accompanied by increased expression of IL6 in the hypothalamus. IL6 induces neurogenesis-related gene expression in the hypothalamus and in neuroprogenitor cells, both from WT as well as from KO mice.
IL6 induces neurogenesis-related gene expression in the hypothalamus of WT mice. In KO mice, the neurogenic actions of IL6 are preserved; however, the appearance of new fully differentiated proopiomelanocortin (POMC) and neuropeptide Y (NPY) neurons is either delayed or disturbed.
在运动过程中产生的白细胞介素-6（IL6）在下丘脑发挥作用，减少与肥胖相关的炎症，并恢复对食物摄入和能量消耗的控制。在海马体中，IL6 的一些有益作用归因于其诱导神经发生的特性。然而，在下丘脑，IL6 的潜在神经发生作用从未被探索过，而其平衡能量摄入的潜力可能是预防或减轻肥胖的一种方法。
使用野生型（WT）和 IL6 敲除（KO）小鼠来研究 IL6 诱导神经发生的能力。我们使用 BrdU 细胞标记、免疫荧光和实时 PCR 来确定神经发生和神经递质标志物的表达。我们从 KO 中制备下丘脑神经祖细胞，并用 IL6 处理，以提供一个体外模型，通过分化实验进一步表征 IL6 的神经发生作用。此外，我们分析了单细胞 RNA 测序数据，并确定了 IL6 和 IL6 受体在小鼠下丘脑特定细胞类型中的表达。
IL6 在下丘脑的表达水平较低，仅限于小胶质细胞和室管膜细胞，而 IL6 受体则在小胶质细胞、室管膜细胞、内皮细胞和星形胶质细胞中表达。外源性 IL6 可减少饮食诱导的肥胖。在外周小鼠中，肥胖抗性伴随着下丘脑 IL6 表达的增加。IL6 诱导 WT 以及 KO 小鼠的下丘脑和神经祖细胞中与神经发生相关的基因表达。
IL6 诱导 WT 小鼠下丘脑与神经发生相关的基因表达。在 KO 小鼠中，IL6 的神经发生作用得以保留；然而，新的完全分化的 proopiomelanocortin（POMC）和神经肽 Y（NPY）神经元的出现要么延迟，要么受到干扰。
