Effect Of High Iodine On Learning And Memory Ability And Hippocampal Neuronal Autophagy In Rats

Iodine is an essential trace element to human body,and either extra or inadequate amount of iodine will impair human health.Iodine deficiency can cause irreversible damage to children's mental development,while appropriate supplement iodine can contribute to the development of intelligence.On the other side,studies have shown that iodine excess has a detrimental effect on children's mental development.Evidence from multiple population-based epidemiological surveys reported that the average level of children intelligence in high iodine areas was significantly lower than that of areas suitable for iodine Results of most animal experiments also confirmed that excessive iodine could reduce the weight of the animal's brain and reduce the ability of learning and memory,of which the underlying mechanism remained unclear.Autophagy is one way of cell metabolism.Normal levels of autophagy can protect cells to a certain extent from harmful conditions and promote cell survival;while rapid or severe autophagy induces programmed cell death.Autophagy plays an important role in the development and maturation of nerve cells.Studies have shown that high levels of iodine can lead to an increase in the level of autophagy in nerve cells,causing damage to them.Objectives:To study the effects of high iodine on learning and memory and hippocampal neuronal autophagy in rats,and toexplore whether there is a connection between the two,in order to further study the mechanism of iodine damage to the nervous system.Methods:36 healthy adult SPF SD rats?male/female=2:1?were selected,after a week of adaptive breeding then mate.The pregnant rats were separately fed and randomly divided into control?tap-water?group and 500,2500 and 5000?g/L KIO₃groups,6 in each group.Rat offsprings were naturally deliveried and the day of birth was marked as 0 day.Nests were standardized on the fourth day after birth,and weaned on the 21st day after birth.The rats were bred in cages of different sex and dosage and continued to be treated with the same exposure as mother mice until the end of 6 months.Part 1:Effect of high iodine on learning and memory in rats Weigh the rats and their thyroid and hippocampus.Determination of urinary iodine by arsenic cerium catalytic spectrophotometry.Levels of serum thyroid hormone were measured by Enzyme-Linked Immunosorbent Assay.Water maze experiment was used to observe the effect of high iodine on learning and memory ability of offspring rats.Part 2:Effect of high iodine on autophagy of rat hippocampal neuronsTransmission electron microscopy was used to observe the ultrastructural changes in the hippocampus of rats.The changes of autophagy-related LC3,Beclin1,p62 genes and protein levels in hippocampal neurons were detected by Reverse Transcription PCR and Western Blot.Results:1 Compared with the control group,body weights of female rats in the KIO₃ exposure group were significantly lower?P<0.05?at the end of the 5th and 6th month after exposure.2 Compared with the control group,the thyroid organ coefficient was significantly reduced among rats in the 500 and 2500?g/L KIO₃ groups,male rats in the 2500?g/L KIO₃ group,and female rats in the 5000?g/L KIO₃ group?P<0.05?;The brain organ coefficient was significantly increased in KIO3 exposure group of females and2500,5000?g/L KIO₃ male rats?P<0.05?.3 The urinary iodine concentration of rats in each group was increased with their corresponding concentration amount of KIO₃ exposure.4 Compared with the control group,the levels of serum TSH,FT₃,and T₄ decreased significantly in the 5000?g/L KIO₃ group of females?P<0.05?,the serum FT₃ in the male rats exposed to 2500 and 5000?g/L KIO₃ was significantly increased?P<0.05?.5 Compared with the control group,the latency of 500?g/L and 5000?g/L KIO₃groups and 2500?g/L KIO₃ male rats increased significantly?P<0.05?,the path of5000?g/L KIO₃ group increased significantly?P<0.05?,and the proportion of pathological pathways in rats exposed to 500 and 2500?g/L KIO₃ decreased?P<0.05?.6 High iodine led to changes in the ultrastructure of hippocampus in rats.Under the transmission electron microscope,the autophagosome with bilayer membrane structure and swollen mitochondria could be seen.And with the increase of iodine exposure dose,vacuolation of cells in the hippocampal neurons,and even demyelination.7 Compared with the control group,the expression of autophagy-related gene Beclin1was significantly decreased among male rats in the 2500?g/L KIO₃ and 5000?g/L KIO₃ groups?P<0.05?.8 Compared with the control group,the level of autophagy-related protein expression in the hippocampus in the 500?g/L KIO₃ group of female rats,the 2500?g/L KIO₃male rats and the 5000?g/L KIO₃ exposure group increased significantly?P<0.05?.The expression level of autophagy-related proteins p62 and Beclin1 in the hippocampus of 2500?g/L KIO₃ group of female rats also increased significantly?P<0.05?.Conclusions:1 High iodine may have a certain degree of neurotoxicity on rats,which can cause a decrease in learning and memory.2 High iodine may cause hippocampal tissue damage in areas associated with learning and memory in rats and lead to the dysfunction of hippocampal neuronal autophagy.The changes of hippocampal neural cell autophagy may be one mechanism of high iodine-induced learning and memory impairment.