Effect of thyroxine on synaptotagmin 1 and SNAP-25 expression in dorsal hippocampus of adult-onset hypothyroid rats.

Adult-onset hypothyroidism causes cognitive dysfunctions of learning and memory, in which many synaptic proteins in hippocampus are involved. In our work, we studied the effect of adult-onset hypothyroidism on the expression of synaptotagmin 1 (syt 1) and SNAP-25 in dorsal hippocampus as well as its recovery by levothyroxine (L-T(4)) replacement therapy. Rats were divided into 4 groups: control, hypothyroidism, and hypothyroid rats treated with 5 μg T(4)/100 g body weight (BW) and 20 μg L-T(4)/100 g BW, respectively. Protein levels of syt 1 and SNAP-25 in dorsal hippocampus were determined by Western blot and immunohistochemistry. The immunoblot analysis indicated that syt 1 was expressed at a significantly lower level in hypothyroid rats, while the level of SNAP-25 was much higher compared to controls. Furthermore, using immunostaining, we found that on the one hand, expression of syt 1 was significantly down-regulated in the examined layers of CA1 and CA3 subregions but not dentate gyrus (DG); however, on the other hand, expression of SNAP-25 was up-regulated in the layers of CA1, CA3, and DG. Two-week treatment with 20 μg LT(4)/ 100 g BW fully restored the levels of syt 1 and SNAP-25 to the normal level, which was more effective than 5 μg LT(4)/ 100 g BW that partially restored the levels of both proteins. These results suggest that adult-onset hypothyroidism caused down-regulation of syt 1 and up-regulation of SNAP- 25 level in dorsal hippocampus, which could be restored by L-T(4) treatment, and the recovery degree is related to the LT(4) dosage.