Neurochemical changes following a single dose of polybrominated diphenyl ether 47 in mice

Abstract

Polybrominated diphenyl ethers (PBDEs) are commonly used as commercial flame retardants in a variety of products, including plastics and textiles. Previous studies in our laboratory, and in the literature, showed that exposure to a specific PBDE congener (PBDE 47) during a critical period of brain development may lead to developmental delays and hyperactivity in adulthood. To date, the underlying causes of these behavioral alterations are unknown, although in vitro studies linked PBDEs with potential alterations in neurotransmitter levels, particularly acetylcholine (ACh) and dopamine (DA). Alterations in DA function have also been noted in cases of hyperactivity in rodents and humans. The current study examined monoamine levels in male mice acutely exposed to corn oil vehicle or PBDE 47 (1, 10, or 30 mg/kg) on postnatal day (PND) 10. Animals were sacrificed on PND 15, PND 20, and in adulthood (131-159 days old). The cortex, striatum, and cerebellum were isolated and analyzed by high-performance liquid chromatography to determine the concentration of monoamines within each brain region. A statistically significant increase in DA levels was seen within the cortex, regardless of age, but only in the 10-mg/kg PBDE treatment group. While these effects did not show a monotonic dose response, we previously reported hyperactivity in littermates in the same dose group, but not at the lower or higher dose. Thus, early developmental exposure to PBDE 47 alters the levels of cortical DA in male mice, which may correlate with behavioral observations in littermates.

A mechanistic view of polybrominated diphenyl ether (PBDE) developmental neurotoxicity

“…Recently, Bradner et al (2013a) confirmed the ability of DE-71 to inhibit vesicular dopamine uptake (IC 50 = 2.8 μM); these investigators also showed that repeated exposures of young mice to DE-71 decreased striatal dopamine levels and expression of the dopamine transporter and the vesicular monoamine transporter 2, which were accompanied by locomotor deficits. An increase of dopamine level were in contrast found in the cerebral cortex of mice exposed to a single 10 mg/kg does of BDE-47 on PND 10 (Gee et al 2011). Increases and decreases in brain dopamine in animals exposed during early development or at a later age had been reported also with PCBs (Fonnum and Mariussen, 2009).…”

The brominated flame retardant BDE-47 causes oxidative stress and apoptotic cell death in vitro and in vivo in mice

“…Male Gclm +/+ and Gclm −/− mice were treated by gavage with BDE-47 on PND 10, according to a dosing protocol utilized by various research groups and one that has been shown to cause long-lasting behavioral and biochemical effects (Eriksson et al 2001; Dingemans et al 2007; Gee and Moser, 2008; Gee et al 2011). Mice were sacrificed after 24 h for a number of biochemical assays.…”

“…Control animals were given corn oil only by gavage (1 ml/kg). The dose was selected on the basis of previous studies showing developmental neurotoxicity upon single postnatal exposures (Eriksson et al 2001; Viberg et al 2003; Dingemans et al 2007; Gee and Moser, 2008; Gee et al 2011). On PND 11 (24 h after exposure) mice were sacrificed and cerebellum and liver were collected for biochemical assays and measurement of BDE-47 levels.…”

Spatial learning and memory deficit of low level polybrominated diphenyl ethers-47 in male adult rat is modulated by intracellular glutamate receptors

“…These adverse effects can also give rise to irreversible changes in adult brain function (Viberg et al, 2003(Viberg et al, , 2006(Viberg et al, and 2007. However, to date the underlying causes of these behavioral and functional alterations are unknown, though in vitro studies have linked PBDEs with potential alterations in neurotransmitter levels, particularly glutamate and dopamine (Mariussen and Fonnum, 2003;Dreiem et al, 2010;Gee et al, 2011). Furthermore, several animal studies revealed effects of PBDEs on neurotransmitter receptor function and brain key protein levels, mainly by hypoactive responses to neurotransmitter receptor agonists.…”