Perinatal exposure to PBDE-47 decreases brain glucose metabolism in male adult rats: Associations with shifts in triiodothyronine and neurobehavior

The brominated flame retardant 2, 2′, 4, 4′-tetrabromodiphenyl ether (PBDE-47) is well known as a developmental neurotoxicant, yet the underlying mechanisms remain elusive. Increasing evidence has demonstrated that brain glucose metabolism perturbation plays a role in neural impairments. Nevertheless, whether this disturbance is involved in PBDE-47-induced neurotoxicity remains unknown. To explore the impacts of perinatal PBDE-47 exposure on brain glucose metabolism, and its link to thyroid hormones (THs) levels as well as neurobehavioral changes. Female Sprague-Dawley rats were orally exposed to PBDE-47 at environmentally relevant levels (0.1, 1.0, and 10.0 mg/kg bw) from pre-pregnancy through weaning of offspring. The male offspring were continued to raise to 88 days after birth for follow-up experiments. Morris water maze and Open field tests were performed to assess the neurobehavioral alterations. The brain glucose metabolism was evaluated using 18 F-labeled fluorodeoxyglucose ( 18 F-FDG) positron emission tomography. Serum THs levels were measured via enzyme-linked immunosorbent assay. Perinatal exposure to PBDE-47 induced neurobehavioral impairments in adult male rats as evidenced by learning and memory impairments, hyperactivity and anxiety-like behavior. Moreover, positron emission tomography showed that the glucose metabolism in the whole and the specific brain regions were markedly declined. Interestingly, variations in brain glucose metabolism were associated with the increased serum triiodothyronine (T 3 ) levels, and both were linked to neurobehavioral disorders. Exposure to environmentally related levels of PBDE-47 at critical developmental stages lowers glucose metabolism in the whole brain and in various brain regions, which is associated with behavioral and cognitive deficits in adult male rats. Moreover, the association may be influenced by the disturbance of T 3 homeostasis. • Perinatal exposure to PBDE-47 induced neurobehavioral deficits in adult male rats. • PET showed that PBDE-47 decreased global and regional brain glucose metabolism. • PBDE-47 disrupted thyroid function by elevating serum triiodothyronine (T 3 ) levels. • Serum T 3 levels alteration was related to brain glucose metabolism disturbance. • Shifts in glucose metabolism and T 3 levels were linked to neurobehavioral defects.