Bisphenol-A exposure during adolescence leads to enduring alterations in cognition and dendritic spine density in adult male and female rats

Abstract

We have previously demonstrated that adolescent exposure of rats to bisphenol-A (BPA), an environmental endocrine disrupter, increases anxiety, impairs spatial memory, and decreases dendritic spine density in the CA1 region of the hippocampus (CA1) and medial prefrontal cortex (mPFC) when measured in adolescents in both sexes. The present study examined whether the behavioral and morphological alterations following BPA exposure during adolescent development are maintained into adulthood. Male and female, adolescent rats received BPA, 40μg/kg/bodyweight, or control treatments for one week. In adulthood, subjects were tested for anxiety and locomotor activity, spatial memory, non-spatial visual memory, and sucrose preference. Additionally, stress-induced serum corticosterone levels and dendritic spine density in the mPFC and CA1 were measured. BPA-treated males, but not females, had decreased arm visits on the elevated plus maze, but there was no effect on anxiety. Non-spatial memory, object recognition, was also decreased in BPA treated males, but not in females. BPA exposure did not alter spatial memory, object placement, but decreased exploration during the tasks in both sexes. No significant group differences in sucrose preference or serum corticosterone levels in response to a stress challenge were found. However, BPA exposure, regardless of sex, significantly decreased spine density of both apical and basal dendrites on pyramidal cells in CA1 but had no effect in the mPFC. Current data are discussed in relation to BPA dependent changes, which were present during adolescence and did, or did not, endure into adulthood. Overall, adolescent BPA exposure, below the current reference safe daily limit set by the U.S.E.P.A., leads to alterations in some behaviors and neuronal morphology that endure into adulthood.

Keywords: Adolescence; Anxiety; Bisphenol-A; Exploration; Memory; Spine density.

Figure 1.

Visits made during elevated plus maze testing. Data is the average ± SEM number of entries made (open, closed, and total arm entries). All significant effects are P<0.05 and significant differences between groups are denoted by *. Significant sex X treatment interactions showed that BPA treated males, but not females, had decreased total visits and decreased visits to the closed arms.

Figure 2.

Object placement performance. All significant effects are P<0.05 and significant differences between groups are denoted by *. In panel A, data are expressed as the total time spent exploring (in seconds, M + SEM) for both the sample (T1) and retention (T2) trials. BPA treated subjects spent less time exploring during T2 than controls. In panel B, data are expressed as the percent of total T2 time spent with the object in the new location (Mean + SEM). No significant group differences were observed in the ratio. Thus, BPA treatment altered exploration but not performance of the spatial memory task.

Figure 3.

Object recognition performance. All significant effects are P<0.05 and significant differences between groups are denoted by *. In panel A, data are expressed as the total time spent exploring (in seconds, M + SEM) for both the sample (T1) and retention (T2) trials. There were no group differences in exploration times. In panel B, data are expressed as the percent of total T2 time spent with the object in the new location (Mean + SEM). A significant sex X treatment interaction showed that discrimination between old and new objects was decreased in BPA treated males, but unaffected in females.

Figure 4.

Photomicrograph illustrating Golgi impregnated secondary basal dendrites from CA1 pyramidal cells in the dorsal hippocampus from male BPA treated (top) and control (bottom) rats. Taken under oil at 100x. Scale bar = 10µm. Arrows denote spines.

Figure 5.

Basal and apical dendritic spine density in CA1 and mPFC. Entries are the average # spines/10 µm ± SEM. All significant effects are P<0.05 and group differences are denoted by *. Panel A shows that adolescent BPA exposure led to decreased spine density on both basal and apical dendrites in CA1. Panel B shows that there were no significant effect of adolescent BPA exposure in mPFC.