小鼠嗅球中水通道蛋白4表达缺失对抑郁发生的影响

Effects of loss of aquaporin 4 expression in olfactory bulb on the occurrence of depression in mice

目的:观察水通道蛋白4(AQP4)在小鼠嗅球中的表达情况,探讨AQP4表达缺失对小鼠抑郁发生的影响。方法:应用免疫荧光技术观察小鼠嗅上皮和嗅球中AQP4的表达,采用嗅觉电位(E0G)测定比较小鼠的嗅觉差异,悬尾试验(TST)和喷溅试验(ST)检测AQP4基因敲除(AQP4^-/-)小鼠与野生型(WT)小鼠的抑郁样行为,并分析抑郁行为与嗅觉电位的相关性。结果:免疫荧光检测发现AQP4在嗅上皮和嗅球神经纤维层和突触小球层均有不同程度表达;AQP4^-/-与WT小鼠相比,食物性嗅觉电位诱发实验的电位更低(P<0.01);抑郁行为学发现AQP4^-/-小鼠悬尾实验的不动时间较长、第一次梳理背部毛发潜伏时间较长以及梳理时间较短(P<0.01);AQP4^-/-小鼠嗅觉电位与悬尾不动时间、梳理潜伏时间呈负相关(P<0.05),与梳理背部毛发时间呈正相关性(P<0.05)。结论:AQP4表达在小鼠嗅鞘细胞膜上,其表达对于维持嗅觉信号的传递具有重要意义,AQP4基因敲除引起小鼠嗅觉的减退或缺失可能与抑郁的发生有关。

Objective:The expression of aquaporin 4(AQP4)ofactory bulb was observed to investigate the effects of AQP4 on the ocurence of depression in mice.Methods:The expression of AQP4 in the olfactory epithelium and小factory bulb of wild-type(WT)mice versus AQP4 null(AQP4^-/-)mice was observed by immunofluoresc ence stai-ning,and then the olfactory potential differences were determined by odorant-stimulated electro-olfactogram(E0C).Next,their depression behaviors were dected via behavioral experiments involving tail suspension test(TST)and splash test(ST).Finally,the relationship between depression behaviors and EOG levels of them was explored.Results:It was showed that there were differences of expression levels among the olfactory epithelium,olfactory bulb nerve fiber layer and synaptie layer by immunofluorescence staining.And the E0C levels of AQP4^-/-mice showed lower than that of WT mice in fod olactory potential induction experiment(P<0.01).In the behavioral tests,the immobile time of TST and the latent time of first combing of back hair were longer,while the combing time was shorter in AQP4^-/-mice versus WT mice(P<0.01).Meanwhile,the olfactory potential levels of AQP4 mice were negatively correlated with im-mobile time of TST and the latent time of combing(P<0.05),while positively correlated with the time of combing back hair(P<0.05).Conclusion:AQP4 is expressed on mouse olfactory ensheathing cell membranes,and is ex-pression is of great sigificance for maintaining the transmission of olfactory signals.AQP4 gene knockout can cause hy-posmia or even anosphrasia in mice,which may be related to the occurrence of depression.