Effects of dose, administration route, and/or vehicle on decabromodiphenyl ether concentrations in plasma of maternal, fetal, and neonatal rats and in milk of maternal rats.

The effects of route and vehicle on blood and milk levels of decabromodiphenyl ether (DecaBDE; CASRN 1163-19-5) were investigated in the rat to assist in the design and conduct of a developmental neurotoxicity study. Blood plasma and/or milk concentrations were determined in dams, fetuses, and/or nursing pups after repeated DecaBDE administration by gavage throughout gestation or gestation and lactation using corn oil (CO) or soyaphospholipon/Lutrol F 127-water (SPL) as the vehicle. The impact of vehicle on plasma levels was also investigated in pups derived from naive dams after a single postnatal dose. This study reports for the first time fetal and neonatal plasma concentrations concurrent with those of maternal plasma and/or milk. Higher concentrations of DecaBDE were achieved in plasma and in milk with CO than with SPL. Furthermore, pups derived from dams treated with only SPL were lower in body weight, compared with those from dams treated with either CO, CO and DecaBDE, or SPL and DecaBDE. The study further shows that exposure to DecaBDE is relatively consistent across the dose range of 100 to 1000 mg/(kg · day) when administered in CO.

Expression of septin 3 isoforms in human brain.

Septin 3 is a novel member of the septin subfamily of GTPase domain proteins. Human septin 3 was originally cloned during a screening of genes expressed in human teratocarcinoma cells induced to differentiate with retinoic acid. Alternative splicing of the septin 3 gene transcript produces two isoforms, A and B, in the human brain, though their regional expression and physiological function remain to be determined. The purpose of the present study was to identify the expression patterns of human septin 3 isoforms in normal human brain and a human neuroblastoma cell line, SH-SY5Y, after retinoic acid-induced differentiation. The expression and distribution patterns of septin 3 isoforms A and B were similar and resembled that of another septin, CDCrel-1. Septin 3A and 3B were expressed in normal human brain in a region-specific manner, with the highest level in the temporal cortex and hippocampus and the lowest level in the brainstem regions. Prominent immunoreactivity was observed diffusely in the neocortices in association with neuropils and punctate structures suggestive of synaptic junctions. Immunoprecipitation studies revealed that septin 3A, 3B, and CDCrel-1 form a complex in the frontal cortex of human brain. These findings, taken together, suggest that septin 3A and 3B, along with CDCrel-1, play some fundamental role(s) in synaptogenesis and neuronal development.