Estrogen-Induced Memory Enhancements Are Blocked by Acute Bisphenol A in Adult Female Rats: Role of Dendritic Spines

Abstract

Acute effects of bisphenol (BPA), an environmental chemical, on estradiol (17α or β-E2)-dependent recognition memory and dendritic spines in the medial prefrontal cortex and hippocampus were investigated in adult female rats. Ovariectomized rats received BPA 30 min before or immediately after a sample trial (viewing objects), and retention trials were performed 4 h later. Retention trials tested discrimination between old and new objects (visual memory) or locations (place memory). When given immediately after the sample trial, BPA, 1-400 μg/kg, did not alter recognition memory, but 1 and 40 μg/kg BPA, respectively, blocked 17β-E2-dependent increases in place and visual memory. When ovariectomized rats were tested with 17α-E2, 1 μg/kg BPA blocked place memory, but up to 40 μg did not block visual memory. BPA, given to cycling rats at 40 μg/kg, blocked visual, but not place, memory during proestrus when 2 h intertrial delays were given. Spine density was assessed at times of memory consolidation (30 min) and retention (4 h) after 17β-E2 or BPA + 17β-E2. In prefrontal cortex, BPA did not alter E2-dependent increases. In the hippocampus, BPA blocked E2 increases in basal spines at 4 h and was additive with E2 at 30 min. Thus, these novel data show that doses of BPA, below the current Environmental Protection Agency safe limit of 50 μg/kg, rapidly alter neural functions dependent on E2 in adult female rats.

Oral exposure to low-dose of nonylphenol impairs memory performance in Sprague-Dawley rats

“…Some studies reported that estrus cycle affect learning and memory, and emotionality (Frye et al, 2000;Marcondes et al, 2001;Pompili et al, 2010;van Goethem et al, 2012). Furthermore, a number of studies repoted that BPA inhibits the effect of estrogen which is an improvement in learning and memory, and the effects of BPA are dependent on endogenous estrogen (Xu et al, 2011;Inagaki et al, 2012). Our findings showing the effects of oral NP administration on fear-motivated learning and memory and emotionality in female rats may thus be related to the estrogen cycle.…”

Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents

“…This effect is not an artifact of the slice preparation, as several in vivo studies of ovariectomized rats have found that E 2 increased spine density in both CA1 and prefrontal cortex layer II/III within 30 min of a systemic injection (MacLusky et al 2005;Inagaki et al 2012). Moreover, agonists for ERa and ERb increased CA1 dendritic spine density in ovariectomized mice within 40 min of a single systemic injection (Phan et al 2011), indicating a role for both ERa or ERb in rapid E 2 -induced spinogenesis.…”

17β-Estradiol regulates histone alterations associated with memory consolidation and increases Bdnf promoter acetylation in middle-aged female mice

“…Therefore, E 2 -induced changes in cell signaling and epigenetic modifications likely follow a specific time course in order to facilitate memory consolidation. Acute systemic injections of E 2 in young female rats can increase spine density in the hippocampus within 30 min (Inagaki et al 2012), an effect that is ERK-dependent in vitro (Srivastava et al 2008). Our laboratory has shown in young female mice that E 2 increases the phosphorylation of p42 ERK and activates ERK-driven mammalian target of rapamycin (mTOR) protein synthesis pathway 5 min after dorsal hippocampal infusion (Fernandez et al 2008;Boulware et al 2013;Fortress et al 2013b), which suggests a possible increase in synaptogenesis as early as 5 min after infusion.…”