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RESEARCH PRODUCT

PPAR-γ Agonist GW1929 But Not Antagonist GW9662 Reduces TBBPA-Induced Neurotoxicity in Primary Neocortical Cells

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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.