Effects of different iodine levels on brain development and ethology in offspring of EAT rats / 中华地方病学杂志

ABSTRACT

Objective:By establishing a rat model of experimental autoimmune thyroiditis(EAT), to investigate the effects of different iodine intake on the hippocampal morphology, monoamine neurotransmitters and ethology of the offspring of EAT rats.Methods:A total of 60 female and 20 male Lewis rats with a body weight of 50 - 60 g were selected. Female rats were divided into 4 groups (15 rats in each group) with random number table method according to their body weight control group (NI group), thyroglobulin group (Tg group), Tg + high iodine Ⅰ group (Tg + HⅠ group), and Tg + high iodine Ⅱ group (Tg + HⅡ group), and the latter three groups were model groups. The contents of iodine in drinking water of the 4 groups were 100 μg/L, 100 μg/L, 20 mg/L and 200 mg/L, respectively. Rats in the model groups were immunized with porcine thyroglobulin (PTg) subcutaneously at multiple sites, and the NI group was injected with normal saline, once every 2 weeks, 3 times in total. The rats in each group were mated in cages according to the ratio of 3 1 between female and male. After experiment of the offspring, the urine samples of mother rats were collected within the previous week, urinary iodine concentration was determined by As 3+-Ce 4+ catalytic spectrophotometry; then the mother rats were killed, HE staining was used to observe the changes of thyroid histomorphology and the infiltration of inflammatory cells; serum thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) of mother rats were determined by radioimmunoassay. Brain tissues were collected from 7 days old offspring, hippocampal morphology of 7 days old offspring was observed by toluidine blue staining; the contents of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in brain tissues of 7 days old offspring were measured by enzyme-linked immunosorbent assay (ELISA); 30 and 60 days old offspring were used for water maze-location navigation test and open field test. Results:The levels of urinary iodine increased significantly of mother rats in Tg + HⅠ and Tg + HⅡ groups than that in NI group (median, μg/L 35 380.18, 236 847.16 vs 221.43, P < 0.05). HE staining showed that the thyroid tissue of mother rats in Tg, Tg + HⅠ and Tg + HⅡ groups had different degrees of destruction and inflammatory cells infiltration, and the degree of destruction and infiltration increased with the increase of iodine intake. Compared with NI group, the contents of TgAb and TPOAb in serum of mother rats in Tg, Tg + HⅠ and Tg + HⅡ groups were significantly increased(2.118 4 ± 0.675 1, 2.103 0 ± 0.714 1, 2.783 6 ± 1.084 3 vs 0.790 1 ± 0.101 0, P < 0.05; 1.015 8 ± 0.252 8, 1.019 5 ± 0.202 0, 0.936 6 ± 0.183 4 vs 0.692 2 ± 0.111 9, P < 0.05), and the content of TgAb in Tg + HⅡ group was significantly higher than that in Tg and Tg + HⅠ groups ( P < 0.05). Compared with NI group, the number of hippocampal neurons decreased and relative damage occurred in Tg, Tg + HⅠ and Tg + HⅡ groups of the offspring. Compared with NI group, the NE contents in brain tissues of the offspring in Tg, Tg + HⅠ and Tg + HⅡ groups decreased (pg/ml 1 232.01 ± 253.45, 1 197.64 ± 222.46, 1 074.40 ± 366.38 vs 1 733.67 ± 158.12, P < 0.05); there were no significant differences in DA and 5-HT contents in brain tissues of offspring in each group ( P > 0.05). In the water maze-location navigation test, the latency of the Tg + HⅡ group on the 4th day of the 30 days old offspring reaching the platform was significantly longer than that of the NI and Tg groups ( P < 0.05). In the open field test, there was no significant difference in 30 and 60 days old offspring in the latency of moving the original quadrant ( P > 0.05). Conclusions:With the increase of iodine intake, the degrees of thyroid tissue destruction and inflammatory cells infiltration in EAT rats increase, and the levels of TgAb in serum increase significantly. Iodine has certain effects on the hippocampal morphology and the level of monoamine neurotransmitters in the brains of the offspring of EAT rats. The effects of different iodine-induced EAT rats on their offspring's learning, memory and spatial exploration are mainly shown in childhood.