Perinatal Exposure to Pbde-47 Decreases Brain Glucose Metabolism in Male Adult Rats: Associations with Shifts in Triiodothyronine and Neurobehavior

Abstract

Background 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.

Objectives 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.

Methods 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 test were performed to assess the neurobehavioral alterations. The brain glucose metabolism was evaluated using 18F-labeled fluorodeoxyglucose (18F-FDG) positron emission tomography. Serum THs levels were measured via enzyme-linked immunosorbent assay.

Results 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 (T3) levels, and both were linked to neurobehavioral disorders.

Conclusion 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 T3 homeostasis.

Note:
Funding declaration: This work was supported by the National Natural Science Foundation of China (Nos. 82173477 and 81703215), the Tongji Hospital (HUST) Foundation for Excellent Young Scientist (No. 2020YQ19), the Tongji Hospital (HUST) Foundation (No. 2022A04) and the China Postdoctoral Science Foundation (Nos. 2016T90694 and 2015M570643).

Conflict of Interests: All the authors declare no conflict of interests.

Ethical Approval: All animal studies were executed with the approval of the Institutional Animal Care and Use Committee of Tongji Medical College, Huazhong University of Science and Technology.

Keywords: 2, 2', 4, 4'-Tetrabromodiphenyl ether, Brain glucose metabolism, Positron emission tomography, Thyroid hormones, Developmental neurotoxicity