Effects and neuro-toxic mechanisms of 2, 2 ', 4, 4 ', 5, 5 '-hexachlorobiphenyl and endosulfan in neuronal stem cells

Endocrine disrupters are exogenous compounds thought to mimic the action of estrogen or other hormones and influence endocrine activity in the body (J uberg, 2000). These chemicals have adverse effects not only in the reproduc tive system but also in the central nervous system during development and t hroughout life. Polychlorinated biphenyls (PCBs) are a class of environment ally persistent and widespread halogenated hydrocarbons. It has been report ed that PCBs are potential neurotoxicants. Endosulfan is an organochlorine insecticide that is extensively used to control pests in vegetables, cotton , and fruits. To determine the effect of 2, 2', 4, 4' 5, 5', hexachlorobiph enyl(2, 4, 5-HCB) and endosulfan on embryo nervous system, we isolated neur al stem cells from rat brain at embryonic day 17. Isolated neural stem cell s showed pluripotenty. Stem cells could differentiate into neurons and glia . Neurite formation in endosulfan and 2, 4, 5-HCB treated cells. And it app eared to be decreased as compared with that in untreated cells. In order to know the neuro-toxic mechanisms of 2, 4, 5-HCB and endosulfan: in neuronal stem cells, we investigated mitogen-activated protein kinase activity (MAP K) and gap junctional intercellular communication (GJIC). Endosulfan decrea sed the MAPK activity in dose dependent manner. Endosulfan and 2, 4, 5-HCB inhibited GJIC compared to the untreated cell by scrape loading dye transfe r (SL/DT). 2, 4, 5-HCB and endosulfan decreased the expression of connexin 43 in dose dependent manner. These results indicated that 2, 4, 5-HCB and e ndosulfan may inhibit differentiation and proliferation of neural stem cell s and gap junctional intercellular communication which play a crucial role in the maintenance of cellular homeostasis.