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

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.

Keywords: 3xTg-AD; Alzheimer׳s disease; Sexual incentive motivation; olfactory preference.