Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, 169 Newton Road, 3322 PBDB, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, 169 Newton Road, 3322 PBDB, Iowa City, IA 52242, USA; Iowa Neurosciences Institute, University of Iowa Carver College of Medicine, 169 Newton Road, 3322 PBDB, Iowa City, IA 52242, USA.
Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, 169 Newton Road, 3322 PBDB, Iowa City, IA 52242, USA; Iowa Neurosciences Institute, University of Iowa Carver College of Medicine, 169 Newton Road, 3322 PBDB, Iowa City, IA 52242, USA.
Cell Rep. 2022 Aug 23;40(8):111239. doi: 10.1016/j.celrep.2022.111239.
Fibroblast growth factor 21 (FGF21) is a liver-derived endocrine hormone that functions to regulate energy homeostasis and macronutrient intake. Recently, FGF21 was reported to be produced and secreted from hypothalamic tanycytes, to regulate peripheral lipid metabolism; however, rigorous investigation of FGF21 expression in the brain has yet to be accomplished. Using a mouse model that drives CRE recombinase in FGF21-expressing cells, we demonstrate that FGF21 is not expressed in the hypothalamus, but instead is produced from the retrosplenial cortex (RSC), an essential brain region for spatial learning and memory. Furthermore, we find that central FGF21 produced in the RSC enhances spatial memory but does not regulate energy homeostasis or sugar intake. Finally, our data demonstrate that administration of FGF21 prolongs the duration of long-term potentiation in the hippocampus and enhances activation of hippocampal neurons. Thus, endogenous and pharmacological FGF21 appear to function in the hippocampus to enhance spatial memory.
成纤维细胞生长因子 21（FGF21）是一种肝脏来源的内分泌激素，其功能是调节能量平衡和宏量营养素摄入。最近，据报道 FGF21 由下丘脑的室管膜细胞产生和分泌，以调节外周脂质代谢；然而，对大脑中 FGF21 的表达还需要进行严格的研究。我们使用一种在表达 FGF21 的细胞中驱动 CRE 重组酶的小鼠模型，证明 FGF21 不在下丘脑表达，而是由后穹窿皮质（RSC）产生，RSC 是空间学习和记忆所必需的大脑区域。此外，我们发现 RSC 中产生的中枢 FGF21 增强了空间记忆，但不调节能量平衡或糖摄入。最后，我们的数据表明，FGF21 的给药延长了海马体长时程增强的持续时间，并增强了海马体神经元的激活。因此，内源性和药理学 FGF21 似乎在海马体中发挥作用以增强空间记忆。
