Neuronal fibroblast growth factor 22 signaling during development, but not in adults, is involved in anhedonia.
Neuronal fibroblast growth factor 22 signaling during development, but not in adults, is involved in anhedonia.
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发育过程中的神经元成纤维细胞生长因子 22 信号传导与快感缺乏有关，但成人中则不然。
DOI：
10.1097/wnr.0000000000001399
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发表时间：
2020
期刊：
影响因子：
1.7
通讯作者：
Umemori,Hisashi
中科院分区：
文献类型：
--
作者：
Terauchi,Akiko;Durlacher,Emily;Pitino,Julia;Umemori,Hisashi
Growth factor signaling in the brain is implicated in many neuropsychiatric disorders, including depression, autism, and epilepsy. Fibroblast growth factor 22 is a growth factor that regulates excitatory synapse development and neurogenesis in the brain. We have previously shown that adult mice in which fibroblast growth factor 22 is constitutively inactivated in all cells throughout life (fibroblast growth factor 22-null mice) show anhedonia, a core feature of depression in humans, suggesting that fibroblast growth factor 22 signaling contributes to the regulation of affective behavior. Here we asked (1) whether inactivation of fibroblast growth factor 22 specifically in neurons is sufficient to induce anhedonia in mice and (2) whether fibroblast growth factor 22 signaling is important during development or in adults for the regulation of affective behavior. To address these questions, we performed the sucrose preference test, which is used as an indicator of anhedonia, with neuron-specific conditional fibroblast growth factor 22 knockout mice, in which fibroblast growth factor 22 is inactivated in neurons at birth (neonatal-fibroblast growth factor 22-knockout mice) or in adults (adult-fibroblast growth factor 22-knockout mice). We found that neonatal-fibroblast growth factor 22-knockout mice show anhedonia (decreased preference for sucrose), while adult-fibroblast growth factor 22-knockout mice do not. Therefore, neuronal fibroblast growth factor 22 signaling is critical during development, and not in adults, for the regulation of affective behavior. Our work also implies that defects in growth factor-dependent synapse development, neurogenesis, or both may underlie depression of a developmental origin.
