Testosterone and dihydrotestosterone differentially improve cognition in aged female mice

Abstract

Compared with age-matched male mice, female mice experience a more severe age-related cognitive decline (ACD). Since androgens are less abundant in aged female mice compared with aged male mice, androgen supplementation may enhance cognition in aged female mice. To test this, we assessed behavioral performance on a variety of tasks in 22- to 24-mo-old gonadally intact female mice treated for 6 wk with silastic capsules containing either testosterone (T) or dihydrotestosterone (DHT) or empty capsules (placebo). Compared with placebo-treated mice, spatial memory retention in the water maze was enhanced by testosterone treatment, but not DHT treatment. In contrast, DHT treatment improved passive avoidance (PA) retention, while T treatment only did so marginally. These data support that androgen supplementation in old female mice improves cognitive performance differentially depending upon the type of hormone treatment and cognitive task.

Dose- and ApoE Isoform-Dependent Cognitive Injury after Cranial56Fe Irradiation in Female Mice

“…Rabin and Shukitt-Hale (2014) and Raber et al (2005Raber et al ( , 2009Raber et al ( , 2015 reviewed the similarities between the effects of aging and radiation exposure on neuronal and behavioral function and drew attention to the efficacy of natural product anti-oxidants in ameliorating deficits from both causes. In particular, components of berry-rich diets are shown to participate in signaling pathways involved in neurotransmission and plasticity, inflammation, and cell survival such that treatments reducing oxidative stress and inflammation also improve performance in older animals and irradiated subjects.…”

“…The age at evaluation and irradiation affects the responses to charged particles (Rabin et al 2012) and X-rays (Forbes et al 2014). Sex and genotype (e.g., ApoE allele and ATM) are important variables (Acevedo et al 2008;Benice and Raber 2009;Haley et al 2012;Higuchi et al 2002;Villasana et al 2006Villasana et al , 2011Yamamoto et al 2011;Yeiser et al 2013;Johnson et al 2014;Parihar et al 2014). Additionally, observations comparing head only-, body only-, or whole body-irradiated animals demonstrate a significant role for the periphery in determining behavioral responses .…”

Brain sex matters: Estrogen in cognition and Alzheimer’s disease

“…The sex hormone-specific action on cognition is also demonstrated by animal studies, such as testosterone treatment in aged females mice, which enhanced spatial retention in water mazes (male-typical cognition). However, there was no significant improvement in object recognition (female-typical cognition) compared to the placebo treated group [106]. …”

Spatial Learning and Memory in Animal Models and Humans

“…As such, it is not surprising that effects of sex are observed in object recognition and spatial learning and memory requiring navigation in animals as well as humans (53-57), further supported by imaging studies (58,59). For instance, castration decreases spatial memory in wild-type mice (60), but androgen treatment recovers performance in males and increases performance in old female mice (61,62). Furthermore, in mice expressing human apoE4, performance on spatial memory tests is improved with androgen treatment (testosterone or dihydrotestosterone) (63) and with selective androgen receptor modulators (SARMs) treatment (64).…”