Effects Of Cerebellar Development And The Expression Of CaMKⅡ,CaM,CaN In The Cerebellum Of Iodine Deficient And Hypothyroid Pup Rats

ObjectiveThrough gestation and lactation,iodine deficient or hypothyroid dam rats were administered either an iodine-deficient diet or PTU-added drinking water.We have tested whether congenital iodine deficiency and hypothyroidism could regulate expression of CaMKâ…¡,CAM,CaN in pup Cerebellum cortex.To figure out the mechanism that iodine deficiency and hypothyroidism impair functional lesion in pup Cerebellum.MethodsFemale Wistar rats(n=28) aging 2 after pregnancy were randomly divided into four groups:control group,iodine deficient group,hypothyroid-1 group(5ppmPTU) and hypothyroid-2 group(15ppmPTU).The control group was fed a normal diet and tap water during the experiment.The iodine deficient group was fed an iodine-deficient 6diet 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 super-sensitive chemiluminescence immunoassay.The part of the cerebellum was separated from the brain for protein detection by Nissl's staining and immunohistochemistry.Results 1,Effects of iodine deficiency and hypothyroidism on Weights of dam and weights of cerebellum,pup and eye opening.In all three groups of dam rats,dams from iodine-deficient groups were significantly lighter than controls in pregnancy and gestation(P<0.05).Weights of pup and weights of cerebellum from iodine-deficient and 15ppmPTU groups were significantly smaller than controls(P<0.05).Eye opening was delayed in iodine-deficient and 15ppmPTU treatment groups,and the ratio of pups within a litter with both eyes opening was lower than controls in the same time.2,Effects of iodine deficiency and hypothyroidism on cerebellar neural development of pup rats.In the result of Nissl's staining:On PN7,there were no significantly difference in all the groups.On PN14,PN21,PN28 and PN42,Nissl's body expression in 5ppmPTU, 15ppmPTU and iodine-deficient groups were significantly lower than those of controls (P<0.05).On PN21,Nissl's body expression in iodine-deficient groups were significantly lower than those of 5ppmPTU groups(P<0.05).3,Effects of iodine deficiency and hypothyroidism on CaMKâ…¡expression in cerebellar cortex of pup rats.In the result of immunohistochemistry:On PN7,PN 14,PN21 and PN28,CaMKâ…¡expression in 15ppmPTU and iodine-deficient groups were significantly lower than those of controls and 5ppmPTU(P<0.05).On PN42,CaMKâ…¡expression in 15ppmPTU and iodine-deficient groups were significantly lower than those of control groups(P<0.05).4,Effects of iodine deficiency and hypothyroidism on CaM expression in cerebellar cortex of pup rats.In the result of immunohistochemistry:On PN7,CaM expression in iodine-deficient groups were significantly lower than those of controls(P<0.05),on PN14,CaM expression in 15ppmPTU and iodine-deficient groups were significantly lower than those of controls and 5ppmPTU groups(P＜0.05).On PN21,CaM expression in 5ppmPTU,15ppmPTU and iodine-deficient groups were significantly lower than those of controls(P＜0.05),CaM expression in 15ppmPTU and iodine-deficient groups were significantly lower than those of 5ppmPTU group (P＜0.05).On PN28 and PN42,CaM expression in 15ppmPTU and iodine-deficient groups were significantly lower than those of controls and 5ppmPTU group(P＜0.05), CaM expression in iodine-deficient groups were significantly lower than those of 15ppmPTU group(P＜0.05).5,Effects of iodine deficiency and hypothyroidism on CaN expression in cerebellar cortex of pup rats.In the result of immunohistochemistry:On PN7,there were no significantly difference in all the groups.On PN14,CaN expression in iodine-deficient groups were significantly higher than those of controls(P＜0.05).On PN21,CaN expression in 15ppmPTU and iodine-deficient groups were significantly higher than those of controls (P＜0.05).On PN28,CaN expression in 15ppmPTU and iodine-deficient groups were significantly higher than those of controls(P＜0.05),CaN expression in iodine-deficient groups were significantly higher than those of 5ppmPTU group(P＜0.05).On PN42, CaN expression in 15ppmPTU and iodine-deficient groups were significantly higher than those of controls(P＜0.05).Conclusion1,Iodine deficiency and hypothyroidism may effect pups development and lead to the body weights decrease and eye opening delay.2,Iodine deficiency and hypothyroidism change cerebellar nerves development.3,Iodine deficiency and hypothyroidism may reduce the expression of CaMKâ…¡, CaM,and increase the expression of CaN 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 CaMKâ…¡,CaM,and CaN.The changes are likely to impaired synaptic plasticity,effected the formation of normal neural circuit,and resulted in cerebellar development disturbance.