PPAR-γ agonist GW1929 but not antagonist GW9662 reduces TBBPA-induced neurotoxicity in primary neocortical cells

Tetrabromobisphenol A (2,2-bis(4-hydroxy-3,5-dibromophenyl)propane; TBBPA) is a widely used brominated flame retardant. TBBPA induces neuronal damage, but the mechanism by which this occurs is largely unknown. We studied the possible involvement of Peroxisome Proliferator-activated Receptor gamma (PPAR-γ) in TBBPA-induced Apoptosis and toxicity in mouse primary neuronal cell cultures. TBBPA enhanced both, Caspase-3 activity and Lactate Dehydrogenase (LDH) release in neocortical cells after 6 and 24 h of exposition. These data were supported at the cellular level with Hoechst 33342 staining. Immunoblot analyses showed that, compared with control cells, 10 μM TBBPA decreased the expression of PPAR-γ protein in neocortical neurons after 1-24 h of exposure. Co-treatment with TBBPA and GW1929 inhibited the TBBPA-induced Caspase-3 activity, apoptotic body formation, and LDH release as well as TBBPA-induced decrease in PPAR-γ protein expression. Thus, our data support neuroprotective potential of PPAR-γ agonists. The PPAR-γ antagonist GW9662 prevented the TBBPA-induced decrease in PPAR-γ protein level, but it potentiated TBBPA-induced apoptotic and neurotoxic effects, which suggest that the mechanism of TBBPA action in neuronal cells is not only PPAR-γ-dependent. Therefore, further studies of the mechanism of TBBPA action in the nervous system are needed.