Exposure to Bisphenol A Exacerbates Migraine-Like Behaviors in a Multibehavior Model of Rat Migraine

Abstract

Migraine is a common and debilitating neurological disorder suffered worldwide. Women experience this condition 3 times more frequently than men, with estrogen strongly implicated to play a role. Bisphenol A (BPA), a highly prevalent xenoestrogen, is known to have estrogenic activity and may have an effect in migraine onset, intensity, and duration through estrogen receptor signaling. It was hypothesized that BPA exposure exacerbates migraine symptoms through estrogen signaling and downstream activation of nociception related pathways. Utilizing a multibehavior model of migraine in ovariectomized female rats, changes in locomotion, light and sound sensitivity, grooming, and acoustic startle were examined. Furthermore, changes in the expression of genes related to estrogen (ERα, GPR30), and nociception (extracellular signal regulated kinase, ERK, sodium gated channel, Nav1.8, and fatty acid amide hydrolase, FAAH) were studied following behavioral experiments. The following results were obtained: BPA treatment significantly exacerbated migraine-like behaviors in rats. Rats exposed to BPA demonstrated decreased locomotion, exacerbated light and sound aversion, altered grooming habits, and enhanced startle reflexes. Furthermore, BPA exposure increased mRNA expression of estrogen receptors, total ERK mRNA and ERK activation, as well as Nav1.8, and FAAH mRNA, indicative of altered estrogen signaling and altered nociception. These results show that BPA, an environmentally pervasive xenoestrogen, exacerbates migraine-like behavior in a rat model and alters expression of estrogen and nociception-related genes.

Low dose exposure to Bisphenol A alters development of gonadotropin-releasing hormone 3 neurons and larval locomotor behavior in Japanese Medaka

“…We used 20-day old fish, because larvae at this age are still under development and there are minimal changes in endogenous hormone levels associated with sexual maturation, which may in turn affect locomotor activity. Hypoactivity induced by chronic BPA exposure is similar to the previous findings that 1-15 mM BPA significantly decreased touch response and swimming speed in response to light stimulation in zebrafish embryos and that 1-7 day treatment of 500 mg/ kg/day BPA suppressed locomotion with increased expression of ERa in young rodents (Vermeer et al, 2013). Although our results suggest a possible link between BPA-induced hypoactivity and decreased TN-GnRH3 soma sizes in 20 dpf larvae, it is important to emphasize that GnRH3 is not the only neural system on which BPA can exert effects.…”

Behavioral effects and mechanisms of migraine pathogenesis following estradiol exposure in a multibehavioral model of migraine in rat

“…Animals received IS or PBS through the cannula implant. During IS or PBS application, the obturator cap was removed and an internal delivery cannula was placed as previously described (Stucky, et al, 2011, Vermeer, 2014). All animals were weighed before behavioral testing throughout the study.…”

“…The same timeline was followed as previously described (Vermeer, 2014). Briefly, rats were given one week to acclimate following arrival and then were subjected to two days of presurgical baseline testing.…”

“…Previous work in our laboratory has shown that exposure to the environmental estrogen bisphenol A (BPA) leads to exacerbated migraine-like behaviors and elevation in mRNA levels of genes related to estradiol and inflammation signaling (Vermeer, 2014). In order to better understand these outcomes and to further investigate the mechanistic role of estradiol in migraine pathogenesis the following study was carried out.…”

Bisphenol A depresses monosynaptic and polysynaptic reflexes in neonatal rat spinal cord in vitro involving estrogen receptor-dependent NO-mediated mechanisms

“…The impaired spatial and avoidance memory abnormalities persisted even up to adulthood, thus indicating the permanent nature of the effects (Xu et al, 2010). BPA besides having negative effects on the development of brain, behavior and memory, has also been reported to produce negative effects on locomotor activity and exploratory behavior in rats (Goncalves et al, 2010;Vermeer et al, 2014). These activities represent alteration in Ia-a motoneuron synaptic activity.…”