Kim Ah Hyun, Chun Hye Jeong, Lee Seulah, Kim Hyung Sik, Lee Jaewon
Department of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, South Korea.
Laboratory of Molecular Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, South Korea.
Food Chem Toxicol. 2017 Aug;106(Pt A):223-231. doi: 10.1016/j.fct.2017.05.053. Epub 2017 May 28.
Tetrabromobisphenol A (TBBPA) is a brominated flame retardant that is commonly used in commercial and household products, such as, computers, televisions, mobile phones, and electronic boards. TBBPA can accumulate in human body fluids, and it has been reported that TBBPA possesses endocrine disruptive activity. However, the neurotoxic effect of TBBPA on hippocampal neurogenesis has not yet been investigated. Accordingly, the present study was undertaken to evaluate the effect of TBBPA on adult hippocampal neurogenesis and cognitive function. Male C57BL/6 mice were orally administrated vehicle or TBBPA (20 mg/kg, 100 mg/kg, or 500 mg/kg daily) for two weeks. TBBPA was observed to significantly and dose-dependently reduce the survival of newly generated cells in the hippocampus but not to affect the proliferation of newly generated cells. Numbers of hippocampal BrdU and NeuN positive cells were dose-dependently reduced by TBBPA, indicating impaired neurogenesis in the hippocampus. Interestingly, glial activation without neuronal death was observed in hippocampi exposed to TBBPA. Furthermore, memory retention was found to be adversely affected by TBBPA exposure by a mechanism involving suppression of the BDNF-CREB signaling pathway. The study suggests high dose TBBPA disrupts hippocampal neurogenesis and induces associated memory deficits.
四溴双酚A（TBBPA）是一种溴化阻燃剂，常用于商业和家用产品，如电脑、电视、手机和电子板。TBBPA可在人体体液中蓄积，并且有报道称TBBPA具有内分泌干扰活性。然而，TBBPA对海马神经发生的神经毒性作用尚未得到研究。因此，本研究旨在评估TBBPA对成年海马神经发生和认知功能的影响。将雄性C57BL/6小鼠口服给予溶剂或TBBPA（每天20毫克/千克、100毫克/千克或500毫克/千克），持续两周。观察到TBBPA显著且剂量依赖性地降低了海马中新生成细胞的存活率，但不影响新生成细胞的增殖。TBBPA使海马中BrdU和NeuN阳性细胞数量呈剂量依赖性减少，表明海马神经发生受损。有趣的是，在暴露于TBBPA的海马中观察到了无神经元死亡的胶质细胞激活。此外，发现TBBPA暴露通过抑制BDNF-CREB信号通路的机制对记忆保持产生不利影响。该研究表明高剂量TBBPA会破坏海马神经发生并诱导相关的记忆缺陷。
