| Objective:Selenium(Se) is an essential element for creatures. Se deficiency could reduce activities of selenoenzymes, and then cause a series of functional impairment as results, in which the influence on nervous system is most focused recently. Se deficiency is correlated with iodine(I) deficiency closely, and I-deficient areas is always accompanied with Se deficiency. After more than 20 years I-supplement, typical congenital myxedema has almost been controled in our country. However, there are still some deuto-congenital myxedema children remains, of which Se deficiency is thought to be the most possible cause, besides I deficiency, nowadays.Previous studies in Se- and/or I-deficent animal models most focused on parental generation or their first filial generation, and always in their adult stage. To simulate prolonged impairment of people who had lived in Se-, I-deficient areas for generations, especially neurological functional lesion of their children, we established prolonged artificial Se-, I-deficent diets feeded SD rat animal model in serials. It spent almost two years that the rat model had been breeded to fourth filial generation. Third filial generation Se-, I-deficient rats had displayed delayed neural development and low abilities of learning and memory in Morris water maze in some degree, which were indicated to be correlated with EGFR/MAPK signal conduction pathway by our study then.To research neurobiochemical mechanisms of neurological functional lesion caused by prolonged Se, I deficiency in developing offspring rats primarily, activities of antioxidase systems in liver, blood, hippocampus, cortex and cerebelli, and also concentrations of monoamine neurotransmitters in hippocampus, frontal cortex and hypothalamus were studied as following.Methods:Healthy SD rats were divided into 4 groups at random, including (1) Control group (SerO.l-O.S/ig/g, I =0.2jug/g), (2) Se-deficient group(Se- group, Se: 0.02,ag/g, I =0.2/ig/g), (3) I-deficient group (I- group, Se:0.1~0.3//g/g, I:0.04,ug/g) , (4) Se- and I-deficient group (Se-I- group. Se:0.01,Mg/g, I:0.04//g/g) . Rats in each group were given different man-made feeds containing different levels of Se and I, and raised by the time of the fourth generation. Postnatal rats, with the age of four days(P4) and 21 days(P21), in third(F3) and fourth generation(F4) were chosen to be studied as following:1. Glutathione peroxidase(GPx) activitie in blood and liver of F3P4, F3P21, F4P3 and F4P21 rats were detected by DTNB method.2. Stereology parameters, including volume density(Vv), nucleolus/plasm(N/P), shape factor(SF) and amount of cell layers of hippocampus neurocytes, were surveyed in brain paraffin sections of F4P21 rats after Nissl dyeing.3. Activities of GPx and superoxide dismutase(SOD) in hippocampus, cortex and cerebelli of F4P21 rats were detected by DTNB method and XO-NBT method respectively.4. Concentrations of tyrosine(Tyr), norepinephrine(NE), tryptophan(Try), serotonin(5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in hippocampus, frontal cortex and hypothalamus of F4P21 rats were detected by high-performance liquid chromatography with fluorescence detection(HPLC-FLD).Results1. In F3P4, F3P21, F4P3 and F4P21 rats, ?GPx activities in blood and liver in Se-and Sel- group were all obviously less than those in Control and I- group(p<0.01). ? There was no significant difference between GPx activities of F4 and F3 rats in Control and I- group with the same age. However, in Se- and Sel- group, GPx activities of F4 rats were lower than those of F3 rats with the age of both 4 and 21 days in liver, while those of F4 rats were less than those of F3 rats with only theage of 21 days in blood.2. Stereologic study in hippocampus of F4P21 rats showed that compared with Control group, CD SF(P<0.05), N/P(P<0.05) of I- group, and SF(P<0.05), Vv(P<0.01) and amount of cell layers(P<0.05) of Control group rised notably in CA1 region. 0 Vv(P<0.05), amount of cell layers(P<0.05) of I- group, and SF(P<0.01), N/P(P<0.05), Vv(P<0.01) and amount of cell layers(P<0.01) of Sel-group also increased markedly in CA3 region. (3) Amount of cell layers of I-group(P<0.05) and Sel- group(P<0.05) both decreased in DG region. Although, there was no significant difference in each encephalic region, Se- group also showed some tendency like the other two experiment groups.3. GPx activitie of Se- and Sel- group, in hippocampus, cortex and cerebelli of F4P21 rats, all droped strikingly (P<0.01). Though the tendency of SOD activitie was almost the same as that of GPx activitie, there was only in cortex that significant difference was displayed(P<0.01).4. Compared with Control group, concentration of 5-HT, 5-HIAA of Se- group decreased appreciably in hippocampus and frontal cortex, but without statistic difference. Concentration of 5-HT, 5-HIAA of I- group droped in frontal cortex (P5-HT=0.011,P5-HIAA=0.011) and that of 5-HT increased in hypothalamus (P=0.039). Concentration of 5-HT, 5-HIAA of Sel- group droped significantly in hippocampus (P5-HT=0.001, P5-HIAA=0.022) and frontal cortex (P5-HT=0.007, P5-HIAA=0.002), however that of 5-HT in hypothalamus (P=0.011) and that of NE in frontal cortex(P=0.001) and hypothalamus(P=0.002), all increased.Conclusion1. Prolonged deficiency of Se, or both Se and I, would greatly reduce GPx activitie of rats in development phase, which had happened in parental generation and damaged the filial generation even more seriously.2. Prolonged deficiency of Se, I and both Se and I could delay the morphological development of neurocytes in hippocampus with different degrees.3. Prolonged deficiency of Se, or both Se and I, would reduce GPx and SOD activitie in brain, so that the encephalic antioxidase system would be destroyed.4. Prolonged deficiency of I decreased 5-HT system in frontal cortex apparently. And deficiency of both Se and I could not only decrease 5-HT system in hippocampus and frontal cortex significantly, but also increase NE compensationally, which indicated that Se deficiency might enhance the impairment induced by I deficiency.
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