Deletion of fibroblast growth factor 22 (FGF22) causes a depression-like phenotype in adult mice.
Deletion of fibroblast growth factor 22 (FGF22) causes a depression-like phenotype in adult mice.
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DOI：
10.1016/j.bbr.2016.03.047
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发表时间：
2016-07-01
影响因子：
2.7
通讯作者：
Umemori H
中科院分区：
文献类型：
--
作者：
Williams AJ;Yee P;Smith MC;Murphy GG;Umemori H
特异性生长因子诱导兴奋性和抑制性突触的形成和分化，并且对于脑发育和功能是必需的。成纤维细胞生长因子22（FGF22）对于在发育期间指定兴奋性突触（包括在海马中）是重要的。在发育过程中具有FGF22基因缺失（FGF22KO）的小鼠随后在成年期具有较少的海马兴奋性突触。因此，FGF22 KO小鼠对癫痫发作诱导具有抗性。除了在学习中发挥关键作用外，海马体还被认为是调解情绪和焦虑的媒介。在这里，我们探讨了FGF22的缺失是否会改变小鼠的情感，焦虑或社会认知行为。我们发现，相对于对照小鼠，FGF22 KO小鼠在强迫游泳试验中表现出更长的漂浮持续时间和更短的漂浮潜伏期，在悬尾试验中表现出更高的不动性，在蔗糖偏好试验中表现出对蔗糖的偏好降低，这些都提示了抑郁样表型。在其他行为测定（包括运动、焦虑或社会认知测试）中，对照和FGF 22 KO小鼠之间没有观察到差异。这些结果表明FGF22在情感行为中具有新的作用。
Specific growth factors induce formation and differentiation of excitatory and inhibitory synapses, and are essential for brain development and function. Fibroblast growth factor 22 (FGF22) is important for specifying excitatory synapses during development, including in the hippocampus. Mice with a genetic deletion of FGF22 (FGF22KO) during development subsequently have fewer hippocampal excitatory synapses in adulthood. As a result, FGF22KO mice are resistant to epileptic seizure induction. In addition to playing a key role in learning, the hippocampus is known to mediate mood and anxiety. Here, we explored whether loss of FGF22 alters affective, anxiety or social cognitive behaviors in mice. We found that relative to control mice, FGF22KO mice display longer duration of floating and decreased latency to float in the forced swim test, increased immobility in the tail suspension test, and decreased preference for sucrose in the sucrose preference test, which are all suggestive of a depressive-like phenotype. No differences were observed between control and FGF22KO mice in other behavioral assays, including motor, anxiety, or social cognitive tests. These results suggest a novel role for FGF22 specifically in affective behaviors.