Se-speciation investigations at neural barrier (NB)

Introduction: Se-speciation helps for deeper insight into Se-metabolism and transport, important at NB or under neurological diseases. Analytical set-up of hyphenated speciation techniques with 2-D-identification of Se-compounds is described. Then applications at NB in paired serum and cerebrospinal fluid (CSF) samples are reported, finishing with comparison of Se-speciation of neurologically diseased persons vs. controls. Method: Serum and CSF samples were subject to speciation analysis by HPLC-ICP-DRC-MS. For improved species identification Se-species were analysed serially after HPLC by CE-ICP-DRC-MS (2D approach). Result: Paired samples had 58.39 (serum) or 0.86 (CSF , each μg Se/L). Prominent Se-species were selenoprotein-P (SePP), glutathione-peroxidase (GPx), thioredoxinreductase (TrxR), Se(IV) and Se-albumin (Se-HSA). Relationships between Se-species from serum and CSF allowed evaluating Se-species passage across NB: SePP-serum correlated with total Se-serum when > 65 μg/L. SePP-CSF appeared independent from SePP-serum. For anti-oxidative Seenzymes higher correlation factors (r2) were calculated: GPx-serum/GPx-CSF: r2=0.3837 and TrxR-serum/TrxR-CSF: r2=0.6293. No correlation for inorganic Se-compounds was found proving limited representativeness of their circulating levels beyond NB[1]. Se-species-ratios (CSF/serum) were 21.4*10-3 (TrxR) or 8.3*10-3 (GPx), being significantly elevated compared to NB permeability factor 3.8*10-3 (HSA). In a hospital-referred cases-control we investigated Se-species in CSF of patients with amyotrophic lateral sclerosis, compared to reference neurological patients. We found an excess concentration of inorganic Se(IV) and reduced levels of organic Se-compounds among ALS patients[2]. Discussion: ROS-protecting enzymes GPx and TrxR seem to be shuttled across NB to brain/CSF. In ALS etiology overexposure of inorganic Se(IV) together with decreased organic Se-species may be involved in ALS etiology.