Effect of sodium selenite on synaptic plasticity and neurogenesis impaired by hypothyroidism.

AIM OF THE STUDY: We investigated protective effect of sodium selenite (Se) on hypothyroidism-induced impairments in, Morris water maze (MWM), long-term potentiation (LTP) and hippocampal neurogenesis male Wistar rats aged of 2 months. MATERIALS AND METHODS: Hypothyroidism was induced by administration of propylthiouracil (Ptu, 1 mg/kg/d) solution to the rats from postnatal day 60 for 81 days with or without Se (0.5mg/kg/d). Neurogenesis was examined by Ki-67 immunohistochemical staining. Se values on plasma and hippocampus were measured with inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: Measurement of fT3 and fT4 levels confirmed that the fT3 levels, but not fT4, in Ptu-treated rats (5435.44±816.05 fg/ml, p < 0.05) has returned to control values (8721.66±2567.68 fg/ml) by Se treatment (8661.65±711.43 fg/ml). Analysis of learning performance in water escape learning task showed that Se supplementation disappeared memory deficit in Ptu-treated rats as shown by significantly decreased time spent in the target quadrant (33.7±0.24% in control group; 26.1±0.48% in Ptu-group, p < 0.05; 33.9±0.44 in Ptu+Se group), although there was no significant difference among groups in any measurement of learning performance on the last day. Considering LTP, Se supplementation improved the deficit in synaptic plasticity in Ptu-treated rats, as shown by significant increase in the excitatory postsynaptic potential slope (% 243±31 in control group; 172±49 in Ptu-group, p < 0.05; 222±65 in Ptu+Se group) without affecting of the impairment in somatic plasticity. Se supplementation did not improve the decrease in the number of progenitor cells in the subgranular layer (SGL) of dentate gyrus (DG) of Ptu treated rats. CONCLUSIONS: These findings suggest that selenium supplementation in hypothyroid patients may improve learning and memory disorders with different physiological mechanisms.HighlightsSe increased serum fT3 levels and hippocampus Se levels in hypothyroid rats.Se attenuated impairment of population spike-LTP in hypothyroid ratsHypothyroidism disrupts neurogenesis process in the dentate gyrus of hippocampus.Se supplementation could not increase new born cells in hypothyroid rats.

Deficiency but Not Supplementation of Selenium Impairs the Hippocampal Long-Term Potentiation and Hippocampus-Dependent Learning.

Among the chemical factors that have been implicated in the etiology of dementia, recent concern has focused on both increased and decreased exposure to the metalloid selenium (Se). This report describes the molecular, behavioral, and electrophysiological analysis of rats that were fed with Se-free chow and Se-enriched tap water for 21 days. Three groups were produced, feeding them on a deficient diet with different Selenium content. Hippocampus-dependent spatial learning was measured using the water maze. Long-term potentiation (LTP) was recorded in the hippocampal dentate gyrus to assess how memory is formed at the cellular level. Hippocampal Se levels were measured in trained rats by using inductively coupled plasma mass spectrometry. Phosphorylated and total tau levels were measured in whole hippocampus by Western blot. An impairment of learning of rats feeding with Se-deficient diet was accompanied by attenuated LTP, and increased ratio of p231Tau-to- and decreased ratio of p416Tau-to-Tau in the non-stimulated hippocampus, despite no significant change was observed in Se levels of hippocampus and plasma. Se supplementation resulted in an increase in both tissues and an increase in the ratio of p231Tau-to-Tau in the non-stimulated hippocampus but did not change learning performance and LTP. Despite impaired learning and LTP, no group differed in probe trial and in the fraction of phosphorylated tau in LTP-induced hippocampus. Reduced level of selenium would probably result in reduced synaptic plasticity as well as impairment of learning ability, suggesting requirement of Se for normal synaptic function.