Effects Of Cerebellar Development And ERK1/2, CREB Expression In The Cerebellum Of Iodine Deficient And Hypothyroid Pup Rats

ObjectiveIodine is a trace element essential for the synthesis of triodothyronine(T3) and thyroxine(T4).Thyroid hormones play a vital role in the process of early growth and development of most organs,especially the immature cerebellum.Iodine deficiency can result in hypothyroidism,during embryonic stage and neonatal period,hypothyroidism effected cerebellar morphology,showed an impairment of motor coordination, indicating the functional defect of the cerebellum.It has not been clearly to the mechanism that iodine deficiency and hypothyroidism impair cerebellar development.So,it is significant to study correlative mechanismsThrough gestation and lactation,iodine-deficient or hypothyroid dam rats were administered either an iodine-deficient diet or PTU-added drinking water.We had observed the difference of cerebellar morphology and the changes of ERK1/2 and CREB proteins in pup cerebellar cortex.To figure out the mechanism that iodine and thyroid hormone action in brain development.MethodsFemale Wistar rats(n=28) aging 2 after pregenancy were randomly divided into four groups:control group,iodine deficient group,hypothyroid-1 group(5ppm) and hypothyroid-2 group(15ppm).The control group was fed a normal diet and tap water during the experiment.The iodine-deficient group was fed an iodine-deficient diet and tap-water.The hypothyroid-1 group was fed a normal diet and had 5ppm PTU-added water and the hypothyroid-2 group had 15ppm PTU-added water.All the groups were from GD6 through to postnatal day(PN) 28.On PN7,PN14,PN21,PN28,pups in each group were weighed and blood samples were taken for the FT₃,FT₄ and TSH super-sensitive chemiluminescence immunoassay.The part of the cerebellum was separated from the brain for protein detection by silver staining and immunohistochemistry.Results1,Effects of iodine deficiency and hypothyroidism on Weights of dam,pup and cerebellumIn all three groups of dam rats,dams from iodine-deficient groups were significantly lighter than controls in pregancy and gestation(P＜0.05).Weights of pup from iodine-deficient and 15ppm groups were significantly smaller than controls (P＜0.05) from PN3 to PN42.Cerebellum weights of pup from iodine-deficient were significantly lighter than control,5ppm and 15ppm groups On PN14,PN21,PN28 and PN422,Effects of iodine deficiency and hypothyroidism on cerebellar morphology of pup ratsCompared to controls,On PN7,iodine-deficient group didn't have clearly layers; On PN14,external granular cells migrate inward,external granular layer thinning, migratio of external granular cells from iodine-deficient and hypothyroidism groups were delayed;On PN21,disappearance of external granular cells from iodine-deficient and 15 ppm groups were delayed,still to remain two or three layer external granule cells,On PN28 and PN42,molecular layer from 5 ppm,15 ppm and iodine-deficient groups became thinner.3,Effects of iodine deficiency and hypothyroidism on ERK1/2 expression in cerebellar cortex of pup ratsIn the result of immunohistochemistry:on PN7,there were no significantly difference in all the groups.On PN14,PN42,ERK1/2 expression in 5ppm,15ppm and iodine-deficient groups were significantly lower than those of controls(P＜0.05), ERK1/2 expression in 15ppm and iodine-deficient groups were significantly lower than those of 5ppm group(P＜0.05).On PN21,PN28,ERK1/2 expression in 5ppm,15ppm and iodine-deficient groups were significantly lower than those of controls(P＜0.05), EPK1/2 expression in iodine-deficient group were significantly lower than those of 5ppm and 15ppm groups(P＜0.05).4,Effects of iodine deficiency and hypothyroidism on CREB expression in cerebellar cortex of pup ratsIn the result of immunohistochemistry:on PN7,there were no significantly difference in all the groups.On PN14,CREB expression in 5ppm,15ppm and iodine-deficient groups were significantly lower than those of controls(P＜0.05),CREB expression in 15ppm group were significantly lower than those of 5ppm group(P＜0.05). On PN21,CREB expression in 5ppm,15ppm and iodine-deficient groups were significantly lower than those of controls,CREB expression in 15ppm and iodine-deficient groups were significantly lower than those of 5ppm group, iodine-deficient groups were significantly lower than those of 15ppm group(P＜0.05). On PN28,PN42,CREB expression in 5ppm,15ppm and iodine-deficient groups were significantly lower than those of controls(P＜0.05),CREB expression in 15ppm and iodine-deficient groups were significantly lower than those of 5ppm group(P＜0.05).Conclusion1,Iodine deficiency and hypothyroidism may effect pups development and lead to the body weights decrease2,Iodine deficiency and hypothyroidism change cerebellar morphology and hamper cerebellum development.3,Iodine deficiency and hypothyroidism may reduce the expression of ERK1/2, CREB in pup cerebellar cortex.In summary,our results demonstrate that transient exposure to a period of iodine deficiency and hypothyroidism during a period of brain development changed cerebellar morphology and effected the expression of the protein.The changes are likely to impaired synaptic plasticity,effected the formation of normal neural circuit, and resulted in cerebellum development disturbance.