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Exposure of young rats to diphenyl ditelluride during lactation affects the homeostasis of the cytoskeleton in neural cells from striatum and cerebellum

, : Exposure of young rats to diphenyl ditelluride during lactation affects the homeostasis of the cytoskeleton in neural cells from striatum and cerebellum. Neurotoxicology 33(5): 1106-1116

In the present report we examined the effect of maternal exposure to diphenyl ditelluride (PhTe)2 (.1mg/kg body weight) during the first 14 days of lactational period on the activity of some protein kinases targeting the cytoskeleton of striatum and cerebellum of their offspring. We analyzed the phosphorylating system associated with glial fibrillary acidic protein (GFAP), and neurofilament of low, medium and high molecular weight (NF-L, NF-M and NF-H, respectively) of pups on PND 15, 21, 3 and 45. We found that (PhTe)2 induced hyperphosphorylation of all the proteins studied on PND 15 and 21, recovering control values on PND 3 and 45. The immunocontent of GFAP, NF-L, NF-M and NF-H in the cerebellum of 15 day-old pups was increased. Western blot assays showed activation/phosphorylation of Erk1/2 on PND 21 and activation/phosphorylation of JNK on PND 15. Otherwise, p38MAPK was not activated in the striatum of (PhTe)2 exposed pups. On the other hand, the cerebellum of pups exposed to (PhTe)2 presented activated/phosphorylated Erk1/2 on PND 15 and 21 as well as activated/phosphorylated p38MAPK on PND 21, while JNK was not activated. Western blot assays showed that both in the striatum and in the cerebellum of (PhTe)2 exposed pups, the immunocontent of the catalytic subunit of PKA (PKAc?) was increased on PND 15. Western blot showed that the phosphorylation level of NF-L Ser55 and NF-M/NF-H KSP repeats was increased in the striatum and cerebellum of both 15 and 21 day-old pups exposed to (PhTe)2. Diphenyl diselenide (PhSe)2, the selenium analog of (PhTe)2, prevented (PhTe)2-induced hyperphosphorylation of striatal intermediate filament (IF) proteins but it failed to prevent the action of (PhTe)2 in cerebellum. Western blot assay showed that the (PhSe)2 prevented activation/phosphorylation of Erk1/2, JNK and PKAc? but did not prevent the stimulatory effect of (PhTe)2 on p38MAPK in cerebellum at PND 2In conclusion, this study demonstrated that dam exposure to low doses of (PhTe)2 can alter cellular signaling targeting the cytoskeleton of striatum and cerebellum in the offspring in a spatiotemporal manner, which can be related to the neurotoxic effects of (PhTe)2. Dam exposure to low doses of diphenyl ditelluride causes neurotoxicity in their offspring. Diphenyl ditelluride via maternal milk targets phosphorylating/dephosphorylating pathways in striatum and cerebellum of pups Diphenyl ditelluride disrupts cerebellary and striatal cytoskeleton of suckling pups exposed via milk Diphenyl ditelluride alters cellular signaling targeting the cytoskeleton of neural cells of pups via maternal milk. Diphenyl diselenide partially prevented the neurotoxic effects of diphenyl ditelluride.


PMID: 22705628

DOI: 10.1016/j.neuro.2012.06.003

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