PDF(Pubmed)
Abstract：
Convergent lines of evidence indicate a striking correlation between olfactory deficits and depressive symptoms. However, the effectiveness of intranasal treatment of antidepressant or other neurotrophic agents remains poorly understanding. Here in this study, we created depression mouse model and explored the antidepressant effects of GLP-1 analog lixisenatide (LXT) with intranasal treatment. Consecutive intranasal treatment of LXT remarkably reduced the depressive and anxiety behaviors. Meanwhile, it also improved the olfactory memory and olfactory sensitivity. Immunofluorescent analysis demonstrated the LXT improved the adult neurogenesis in olfactory system and hippocampus. Inhibition of adult neurogenesis with TMZ caused the compromised effects of LXT in improving emotional and olfactory functions, suggesting the vital role of adult neurogenesis in LXT induced depression therapeutic effects. Treatment of LXT resulted in the increased phosphorylation of CREB protein in hippocampal tissue, indicating CREB plays important roles in antidepressant effects of LXT intranasal treatment. Inhibiting CREB with chemical approach decreased effects of LXT in reserving depression induced emotional and olfactory functions. In conclusion, our study suggests intranasal treatment of LXT could be a potential antidepressant to improve the olfactory functions as well as the emotional behaviors.
摘要：
趋同的证据表明，嗅觉缺陷和抑郁症状之间存在显着相关性。然而,抗抑郁药或其他神经营养药的鼻内治疗的有效性仍然知之甚少。在这项研究中，我们创建了抑郁症小鼠模型,并探讨了GLP-1类似物利西拉来(LXT)经鼻内治疗的抗抑郁作用.连续鼻内治疗LXT可显着降低抑郁和焦虑行为。同时,它还提高了嗅觉记忆和嗅觉灵敏度。免疫荧光分析表明，LXT改善了嗅觉系统和海马中的成年神经发生。用TMZ抑制成人神经发生导致LXT在改善情绪和嗅觉功能方面的作用受损，提示成人神经发生在LXT诱导的抑郁症治疗效果中的重要作用。LXT治疗导致海马组织CREB蛋白磷酸化增加，提示CREB在LXT鼻内治疗的抗抑郁作用中起重要作用。用化学方法抑制CREB可降低LXT在保留抑郁症诱导的情绪和嗅觉功能中的作用。总之,我们的研究表明，鼻内治疗LXT可能是一种潜在的抗抑郁药，可以改善嗅觉功能和情绪行为。
