Developmental PCB exposure increases susceptibility to audiogenic seizures in adulthood

Abstract

Developmental exposure to polychlorinated biphenyls (PCBs) causes auditory deficits. Thus, we recently conducted a study to investigate if developmental PCB exposure would exacerbate noise-induced hearing loss in adulthood. Unexpectedly, some PCB-exposed rats exhibited seizure-like behaviors when exposed to loud noise. Therefore, we conducted the current experiment to determine if adult rats perinatally exposed to PCBs are more susceptible to audiogenic seizures when tested in a standard audiogenic seizure paradigm. Adult male and female rats exposed to PCBs during gestation and lactation (0, 1, 3 or 6 mg/kg/day) and previously tested in the noise-induced hearing loss study were presented with a 100dB noise stimulus. If they did not exhibit clonus in response to the 100dB noise, they were exposed to a 105dB stimulus 24-48 hours later. This was followed by an 110dB stimulus 24-48 hours later if they did not exhibit clonus at 105 dB. Female and male rats exposed to either 3 or 6 mg/kg PCBs exhibited a significantly higher incidence of audiogenic seizures, shorter latency to onset of seizures, and greater severity of seizures compared to controls. Thyroxine measured in littermates at weaning was significantly lower in all PCB groups compared to controls, suggesting a potential mechanism for the increased incidence of audiogenic seizures. This is the first study to show that developmental PCB exposure increases the susceptibility to audiogenic seizures in adulthood.

Developmental exposure to PCBs alters the activation of the auditory cortex in response to GABA A antagonism

“…Previous work from our lab has also demonstrated that PCB exposure during early development leads to an increase in audiogenic seizure incidence, a decrease in the latency to onset of audiogenic seizures, and an increase in the severity of seizures in adult male and female rats (Poon et al, 2015). Importantly, these effects were observed in mature adult rats many months after PCB exposure ended, suggesting that PCB exposure altered developmental processes, leading to a permanent increase in susceptibility to audiogenic seizures.…”

“…Maternal exposure to the same mixture and dose of PCBs used in this study dramatically reduces circulating levels of thyroxine in the offspring (Poon et al, 2015). Although it is unknown if decreased levels of thyroxine contribute to later changes in flavoprotein activation in the AC, it is known that thyroid hormones are integral to the normal development and later functioning of the auditory system (Crofton and Zoeller, 2005; Melse-Boonstra and Mackenzie 2013, Ng et al, 2013) and are important for the normal development of white matter and establishment of layers within the cortex (Gilbert et al, 2014; Berbel et al, 2001).…”

“…Developmental PCB exposure alters function of the outer hair cells in the cochlea, decreases GAD levels in the IC, and increases the incidence of audiogenic seizures in adult rats (Bandara et al, 2016; Poon et al, 2015; Powers et al, 2006; 2009). Additionally, chronic gestational exposure to an individual PCB congener (PCB95) leads to significant changes in the tonotopic organization of the AC, as well as the receptive fields, and the best frequencies to elicit excitation and inhibition in the AC (Kenet al, 2007).…”

“…The mixture consisted of 35% Aroclor 1242 (Monsanto lot KB 05-415; St. Louis, MO), 35% Aroclor 1248 (Accustandard lot F-110; New Haven, CT), 15% Aroclor 1254 (Monsanto lot KB 05-612), and 15% Aroclor 1260 (Accustandard lot 021-020) (Kostyniak et al, 2005). The dose of 6 mg/kg PCBs was selected for this study based on previous studies demonstrating ototoxicity and increased incidence of audiogenic seizures (Powers et al, 2006, Poon et al, 2011; 2015) at this dose, without other overt signs of clinical toxicity (Kostyniak et al,. 2005).…”

Developmental exposure to an environmental PCB mixture delays the propagation of electrical kindling from the amygdala

“…Recently our laboratory found that developmental exposure of rats to PCBs caused an increase in audiogenic seizure (AGS) susceptibility in adulthood (Poon et al ., 2015; Bandara et al ., 2016). Adult offspring of dams administered PCBs during gestation and lactation exhibited increased AGS incidence and severity compared to controls upon exposure to a 100 dB SPL noise.…”