Olfactory dysfunction is related with various neurodegenerative and neuropsychiatric disorders such as Alzheimer's disease and Parkinson's disease, which show impaired cognitive functions. However, the effects of olfactory dysfunction on hippocampal dependent learning and memory remain elusive. In this study, mice were treated with intranasal zinc sulfate (ZnSO₄) infusion which resulted in a complete but reversible loss of olfactory function. Olfaction was totally destroyed even 1 week after zinc sulfate treatment, but partially recovered 4 weeks later. We found learning and memory in Y-maze and fear conditioning were not affected by ZnSO₄ 1 week after the treatment, but learning and memory were severely destroyed 4 weeks later. Electrophysiology results showed impaired hippocampal long-term potentiation and long-term depression 4 weeks after the olfaction dysfunction, while only long-term depression was impaired 1 week after the treatment. Western blot showed that the expression and phosphorylation of GluA1 in zinc group did not show any increase after fear conditioning as the control mice. Serum corticosterone release was increased in olfactory deficit mice at baseline and after acute stress when tested 3, 10 and 20 days after the olfactory dysfunction. All these results indicated that reversible olfactory dysfunction elicited impaired hippocampal function in mice. The higher corticosterone release after olfactory deficiency might serve as an underling mechanism.

嗅觉功能障碍与各种神经退行性疾病和神经精神疾病有关，如阿尔茨海默病和帕金森病，表现为认知功能受损。然而，嗅觉功能障碍对海马依赖性学习和记忆的影响仍然难以捉摸。在这项研究中，小鼠接受鼻内硫酸锌 (ZnSO ₄ ) 输注治疗，导致嗅觉功能完全但可逆的丧失。硫酸锌处理1周后嗅觉完全消失，4周后部分恢复。我们发现 Y 迷宫中的学习和记忆以及恐惧条件反射不受 ZnSO _{4 的}影响治疗后1周，但4周后学习和记忆严重受损。电生理结果显示，嗅觉功能障碍后4周海马长时程增强功能受损和长期抑郁，而治疗后1周仅长期抑郁受损。Western blot结果显示，锌组GluA1的表达和磷酸化与对照组小鼠相比在恐惧条件化后没有表现出任何增加。在嗅觉功能障碍后 3、10 和 20 天进行测试时，嗅觉缺陷小鼠在基线和急性应激后的血清皮质酮释放增加。所有这些结果表明，可逆性嗅觉功能障碍引起小鼠海马功能受损。嗅觉缺乏后较高的皮质酮释放可能是一种潜在的机制。