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阿尔茨海默病转基因3xTg-AD雌性小鼠模型中嗅觉引导行为的缺陷。

Deficits in odor-guided behaviors in the transgenic 3xTg-AD female mouse model of Alzheimer׳s disease.

作者信息

Coronas-Sámano G, Portillo W, Beltrán Campos V, Medina-Aguirre G I, Paredes R G, Diaz-Cintra S

机构信息

Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus UNAM Juriquilla, Querétaro, Mexico.

División de Ciencias de la Salud e Ingenierías, Universidad de Guanajuato, Campus Celaya Salvatierra, Mexico.

出版信息

Brain Res. 2014 Jul 14;1572:18-25. doi: 10.1016/j.brainres.2014.05.013. Epub 2014 May 16.

DOI:10.1016/j.brainres.2014.05.013
PMID:24842003
Abstract

Alzheimer׳s disease (AD) is characterized by a number of alterations including those in cognition and olfaction. An early symptom of AD is decreased olfactory ability, which may affect odor-guided behaviors. To test this possibility we evaluated alterations in sexual incentive motivation, sexual olfactory preference, sexual olfactory discrimination, nursing-relevant olfactory preference and olfactory discrimination in female mice. We tested 3xTg-AD (a triple transgenic model, which is a "knock in" of PS1M146V, APPSwe, and tauP300L) and wild type (WT) female mice when receptive (estrous) and non-receptive (anestrous). Subjects were divided into three groups of different ages: (1) 4-5 months, (2) 10-11 months, and (3) 16-18 months. In the sexual incentive motivation task, the receptive 3xTg-AD females showed no preference for a sexually active male at any age studied, in contrast to the WT females. In the sexual olfactory preference test, the receptive WT females were able to identify sexually active male secretions at all ages, but the oldest (16-18 months old) 3xTg-AD females could not. In addition, the oldest 3xTg-AD females showed no preference for nursing-relevant odors in dam secretions and were unable to discriminate between cinnamon and strawberry odors, indicating olfactory alterations. Thus, the present study suggests that the olfactory deficits in this mouse model are associated with changes in sexual incentive motivation and discrimination of food-related odors.

摘要

阿尔茨海默病(AD)的特征是包括认知和嗅觉在内的多种改变。AD的早期症状之一是嗅觉能力下降,这可能会影响气味引导行为。为了验证这种可能性,我们评估了雌性小鼠在性动机、性嗅觉偏好、性嗅觉辨别、与哺育相关的嗅觉偏好以及嗅觉辨别方面的改变。我们对3xTg-AD(一种三转基因模型,即PS1M146V、APPSwe和tauP300L的“敲入”模型)和野生型(WT)雌性小鼠在发情期和非发情期进行了测试。实验对象被分为三个不同年龄组:(1)4 - 5个月,(2)10 - 11个月,(3)16 - 18个月。在性动机任务中,与WT雌性小鼠不同,处于发情期的3xTg-AD雌性小鼠在所有研究年龄阶段对性活跃雄性均无偏好。在性嗅觉偏好测试中,处于发情期的WT雌性小鼠在所有年龄阶段都能够识别性活跃雄性的分泌物,但年龄最大的(16 - 18个月大)3xTg-AD雌性小鼠却不能。此外,年龄最大的3xTg-AD雌性小鼠对母鼠分泌物中与哺育相关的气味没有偏好,并且无法区分肉桂和草莓气味,这表明存在嗅觉改变。因此,本研究表明该小鼠模型中的嗅觉缺陷与性动机变化以及对食物相关气味的辨别能力有关。

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