Sex dimorphisms in the rate of age-related decline in spatial memory: relevance to alterations in the estrous cycle

Abstract

The present experiments demonstrate the existence of sex differences in the rate of development and the magnitude of age-dependent impairments in cognitive and sensorimotor abilities. Although no sex differences were found in spatial reference memory at a young age, the mnemonic ability of female rats deteriorated more rapidly than that of male rats. A major drop in reference memory of the females occurred at the age of 12 months, whereas in the males the onset of impairments occurred later, at the age of 18 months. In spatial working memory, on the other hand, the magnitude of decline was greater in females than in males, although the onset of these impairments occurred at the age of 24 months in both sexes. A sexual dimorphism-aging interaction also was observed in sensorimotor performance. Up to the age of 18 months the females outperformed the males. Subsequently, by the age of 24 months, the performance of the females declined to a level similar to that of the males. The deficits observed in reference and working memory seem to be cognitive in origin and not attributable to alterations in sensory and motor abilities. In addition, the earlier onset of reference memory impairments in females generally coincides with the onset of alterations in the estrous cycle, suggesting that a decline in the estrogenic milieu of the females could be a factor in accelerating the rate of age-related cognitive impairments in the female rat.

Fig. 1.

Straight Swim test; a comparison of the mean swim time (± SEM) of males and females at four different ages.

Fig. 2.

Place discrimination in the water maze; a comparison of the mean performance (± SEM) of males (filled symbols) and females (open symbols) across sessions in platform trial measures (two left columns): swim time (top), swim distance (center), and heading angle (bottom) and in probe trial measures (two right columns): target quadrant (top), annulus-40 (center), and platform crossings (bottom).

Fig. 3.

Place discrimination in the water maze; a comparison of the session averages (± SEM) of males (solid line) and females (dashed line) across four different ages. Shown are significant sex differences at ***p < 0.001, **p < 0.01, *p<0.05.

Fig. 4.

Repeated acquisition in the water maze; a comparison of the session averages (± SEM) from swim time ratio and swim distance ratio of males and females across four different ages. ***Sex differences at p < 0.001 between 14-month-old males and females.

Fig. 5.

Sensorimotor skills; a comparison of the mean performance (± SEM) of males (solid line) and females (dashed line) across four different ages. Shown are significant sex differences at ***p < 0.001, **p < 0.01, and *p < 0.05, respectively, in the ANOVA and (⊙) at p < 0.05 in the ANCOVA.

Fig. 6.

Comparison of the mean body weight (± SEM) of females and males across four ages. Shown are significant sex differences at ***p < 0.001.

Fig. 7.

Relationship between body weight and performance in sensorimotor tasks in males (solid line) and females (dashed line). The lines represent results from Pearson correlations, significant at p< 0.001. Symbols in the scatter plots represent the data for the individual animals.

Fig. 8.

Regularity of estrous cycle at four different age groups.

Fig. 9.

Place discrimination in the water maze (Target Quadrant measure); a comparison of the session averages (± SEM) of females with a different cyclic status at four different age groups.