Recent evidence highlights the fibroblast growth factor (FGF) family in emotion modulation. Although ligands that activate FGF receptors have antidepressant and anxiolytic effects in animal models, FGF ligands have a broad range of actions both in the brain and the periphery. Therefore, identifying molecular partners that may function as allosteric modulators could offer new avenues for drug development. Since neural cell adhesion molecule (NCAM) activates FGF receptors, we asked whether peripherally administered NCAM peptide mimetics penetrate the brain and alter the behavior of standardized tests that have predictive validity for drug treatments of anxiety or depression. The NCAM peptide mimetic, plannexin, acutely increased and chronically decreased anxiety, but did not have antidepressant effects in rats. Another NCAM peptide mimetic, FGLL, had acute anxiogenic effects and chronic antidepressant effects in rats. A related NCAM peptide mimetic, FGLS, had antidepressant effects without modulating anxiety-like behavior, and these antidepressant effects were blocked by an AMPA receptor antagonist. Cisternal cerebrospinal fluid (CSF) levels of FGLs correlated with blood plasma levels in rats and non-human primates, and CSF-to-blood ratios of FGLS were comparable in both species. Results indicate that NCAM peptide mimetics penetrate the brain and support the suggestion that FGLS may be a candidate for further development as a novel treatment for major depressive disorder in humans.

中文翻译：

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神经细胞粘附分子肽模拟物调节情绪：大鼠和非人类灵长类动物的药代动力学和行为研究。

最近的证据强调了情绪调节中的成纤维细胞生长因子 (FGF) 家族。尽管激活 FGF 受体的配体在动物模型中具有抗抑郁和抗焦虑作用，但 FGF 配体在大脑和外周都有广泛的作用。因此，识别可能作为变构调节剂的分子伴侣可以为药物开发提供新的途径。由于神经细胞粘附分子 (NCAM) 激活 FGF 受体，我们询问外周给药的 NCAM 肽模拟物是否会穿透大脑并改变对焦虑或抑郁的药物治疗具有预测有效性的标准化测试的行为。NCAM 肽模拟物 plannexin 急性增加和长期减少焦虑，但在大鼠中没有抗抑郁作用。另一种 NCAM 肽模拟物 FGLL，对大鼠有急性焦虑作用和慢性抗抑郁作用。相关的 NCAM 肽模拟物 FGLS 具有抗抑郁作用，但不会调节焦虑样行为，这些抗抑郁作用被 AMPA 受体拮抗剂阻断。FGL 的脑脊液 (CSF) 水平与大鼠和非人类灵长类动物的血浆水平相关，并且 FGLS 的脑脊液与血液的比率在两个物种中具有可比性。结果表明，NCAM 肽模拟物穿透大脑并支持 FGLS 可能成为进一步开发作为人类重度抑郁症新疗法的候选者的建议。并且这些抗抑郁作用被AMPA受体拮抗剂阻断。FGL 的脑脊液 (CSF) 水平与大鼠和非人类灵长类动物的血浆水平相关，并且 FGLS 的脑脊液与血液的比率在两个物种中具有可比性。结果表明，NCAM 肽模拟物穿透大脑并支持 FGLS 可能成为进一步开发作为人类重度抑郁症新疗法的候选者的建议。并且这些抗抑郁作用被AMPA受体拮抗剂阻断。FGL 的脑脊液 (CSF) 水平与大鼠和非人类灵长类动物的血浆水平相关，并且 FGLS 的脑脊液与血液的比率在两个物种中具有可比性。结果表明，NCAM 肽模拟物穿透大脑并支持 FGLS 可能成为进一步开发作为人类重度抑郁症新疗法的候选者的建议。