Experimental Study Of Long-term Synaptic Plasticity And PKC Activity And GAP-43 Expression In The Hippocampus Of Iodine Deficient And Hypothyroid Pup Rats

ObjectiveThrough gestation and lactation, iodine deficient or hypothyroid dam rats were administered either an iodine - deficient diet dr methimazole - added drinking water. We have tested whether congenital iodine deficiency and hypothyroidism could regulate protein kinase C ( PKC ) , growth - associated protein - 43 ( GAP -43) and long - term potentiation ( LTP) in pup hippocampus. To figure out the mechanism that iodine deficiency and hypothyroidism impair long - term synaptic plasticity and learning and memory.MethodsFemale Wistar rats (N = 45 ) aging 2 months were obtained from the Center of Experimental Animals, China Medical University. Female rats were randomly divided into three groups (n =15 each) ; control group, iodine deficient group, and hypothyroid group. Animals were observed for one week before mating. The day a vaginal plug was identified was taken as gestational day (GD) 0. 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 deionized - water from one week prior to mating through to postnatal day (PN) 30. The hypothyroid group was fed a normal diet and had methimazole - added water from GD10 to PN30. On PN20 and PN30, 10 pups in each group were weighed and blood samples were taken for the FT3 and FT4 radioimmunoassay ( RIA). The part of the hippocampus was separated from the brain for PKC activity detection onPN30. The brains were immersed with 4% paraformaldehyde for histological and immunochemistrical assays. On PN60, 10 pups from each group were used for in vivo electrophysiological assessments of the CAl area. Following LTP - induction , only the pups with good responses were weighed and blood sampled for RIA. The brains were removed for immunochemistrical assavs.Results1. Pup body weight and thyroid hormone levels; For the pup rats, pups from iodine deficient and hypothyroid groups were significantly smaller than controls on PN20, PN30 and PN60 (P <0. 01) ; The concentrations of serum FT3 and FT4 in both treated groups were also significantly lower than controls (P <0. 01).2. Effects of iodine deficiency and hypothyroidism on PKC activity-. The cytosol PKC activities in both treated groups were significantly lower than those of controls. However, PKC activities in the membrane were significantly higher than those of controls (P < 0.05).3. Effects of iodine deficiency and hypothyroidism on GAP - 43 expression : On PN30 and PN60, the distributions of GAP - 43 expression in iodine deficient and hypothyroid groups were consistent with that of the control group. However, the intensity of staining and expression of GAP - 43 in both treated groups were lower than those of controls. IOD total of GAP -43 in the hippocampus area CAl of iodine deficient and hypothyroid rats was significantly lower than control (P<0.01).4. Effects of iodine deficiency and hypothyroidism on long - term synaptic plasticities: PS amplitude and f - EPSP slope in iodine deficient and hypothyroid groups were significantly lower than those in control group (P <0. 01). The occurrences of LTP in iodine deficient and hypothyroid groups were significantly lower than that of the control group (P <0. 05) , and the occurrences of LTD in both treated groups were higher than that of the control group.