Polychlorinated biphenyl (PCBs) mixtures contain a number of different congeners, some of which have been proposed to be neuroactive. Recent studies have suggested that orthesubstituted PCBs may be neuroactive, while 'dioxin-like' non-orthesubstituted congeners are not. This study compared the in vitro effects of a putative neuroactive orthebiphenyl (Z,Z'-dichlorobiphenyl; DCBP) with that of a putative non-neuroactive congener lacking orthechlorine substitutions (3,3' ,4,4,5-pentachlorobiphenyl; PCBP) on Mgz+ -ATPase activity in mitochondrial and synaptosomal preparations from striatum, hypothalamus, cerebellum and hippocampus.
In these studies, DCBP significantly inhibited oligomycin-sensitive (0s) Mg2+-ATPase activity in all four brain regions in a concentration-dependent manner; PCBP, on the other hand, had no effect on 0s Mg2+-ATPase activity in any brain region examined at concentrations up to 100 FM. The striatum, a dopamine-rich region, was not preferentially sensitive to the effects of DCBP. Furthermore, DCBP did not inhibit synaptosomal Na'l K+-ATPase activity, suggesting a specificity of action on 0s Mg2+-ATPase. These data support previous structure-activity relationships, suggesting that orthesubstituted PCB congeners are neuroactive while nonorthesubstituted congeners are not. Disruption of mitochondrial oxidative energy production may play a role in the neuroactivity of orthechlorinated PCBs.