Multiple mechanisms of PCB neurotoxicity
- Univ. of New York, Albany, NY (United States); and others
Polychlorinated biphenyls (PCBs) have been implicated in cancer, but many of the symptoms in humans exposed to PCBs are related to the nervous system and behavior. We demonstrated three different direct mechanisms whereby PCBs are neurotoxic in rats. By using flow cytometry, we demonstrated that the orthosubstituted PCB congener 2,4,4{prime}, but neither TCDD nor the coplanar PCB congener 3,4,5,3{prime},4{prime}, causes rapid death of cerebellar granule cells. The ortho-substituted congener 2,4,4{prime} reduced long-term potentiation, an indicator of cognitive potential, in hippocampal brain slices, but a similar effect was observed for the coplanar congener 3,4,3{prime},4{prime}, indicating that this effect may be caused by both ortho- and coplanar congeners by mechanisms presumably not mediated via the Ah receptor. It was previously shown that some ortho-substituted PCB congeners cause a reduction in levels of the neurotransmitter dopamine, and we present in vitro and in vivo evidence that this is due to reduction of synthesis of dopamine via inhibition of the enzyme tyrosine hydroxylase. Thus, PCBs have a variety of mechanisms of primary neurotoxicity, and neurotoxicity is a characteristic of ortho-substituted, non-dioxin-like congeners as well as some coplanar congeners. The relative contribution of each of these mechanisms to the loss of cognitive function in humans exposed to PCBs remains to be determined. 42 refs., 3 figs., 1 tab.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States)
- OSTI ID:
- 567728
- Report Number(s):
- CONF-9611157-; ON: DE97009015; TRN: 98:000722-0031
- Resource Relation:
- Conference: 1996 Pacific Basin conference on hazardous waste, Kuala Lumpur (Malaysia), 4-8 Nov 1996; Other Information: PBD: [1996]; Related Information: Is Part Of Pacific Basin conference on hazardous waste: Proceedings; PB: 706 p.
- Country of Publication:
- United States
- Language:
- English
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