Effect Of Hypothyroidism On The Syntaxin-1 Expression In The Prefrontal Lobe Of Adult Rats And The Affection Of Thyroxine Treatment

Objective To observe the effect of adult-onset hypothyroidism on the expression of syntaxin-1 in the prefrontal lobe and whether the altered proteins could be restored by T4 treatment. Further to explore the molecular mechanism of brain impairment by hypothyroidism.Methods All rats were separated into 4 groups randomly: (1) hypothyroidism rats (PTU group). Twelve hypothyroid rats were induced by daily intraperitoneal injection of 6-n-propyl-2-thiouracil ( PTU, dissolved in saline solution, 1 mg/100 g body weight (BW)) for six weeks; (2) L-T4 treatment rats with small dose (PTU+5-T4 group). Eleven rats were treated with PTU for six weeks as described above. But from the fifth week, they were also treated with intraperitoneally injected L-T4 (dissolved in saline solution, 5μg/100 g BW) every day for two weeks; (3) L-T4 treatment rats with large dose (PTU+20-T4 group). Eleven rats were treated according to the same protocols as the PTU+5-T4 group except increasing the dosage of L-T4 to 20μg/100 g BW; (4) control rats (control group). Eleven control rats were given same volume of saline solution for six weeks with hypothyroidism rats. The radioimmunoassay kits were applied to assay the levels of serum T3 and T4, and immunohistochemical method was used to determine the levels syntaxin-1 in the prefrontal lobe of rats from different groups. All statistical analysis was performed using SPSS software (version 13.0). Values are expressed as mean±S.E.M. The data among the groups were compared using one-way ANOVA. Statistical significance was defined as P < 0.05. Results At the beginning of the study, body weights of the animals were not significantly different. The normal growth of body weight in the control group was increased by 49.0% at the time of the experiment. However, body weight gain in the PTU, PTU+5-T4 and PTU+20-T4 groups increased only by 21.5%, 32.5% and 26.1%, respectively, over the same period of time, which is significantly lower than the controls (P < 0.05).Serum T3,T4 levels of rats in the PTU group were significantly lower than those in the control group (P < 0.05). In the PTU+5-T4 group, the serum T3,T4 levels of rats were similar to those in the control group, that of the PTU+20-T4 group were significantly higher than those in the control group (P < 0.01).Compared to the control group, the syntaxin-1 in the PTU group was significantly decreased in theⅠ,Ⅱ,Ⅲ,Ⅳ,Ⅴlayers of the prefrontal lobe. In the PTU+5-T4 group, syntaxin-1 were restored in all ayers.Conclusion These data suggested that the expression of syntaxin-1 in the prefrontal lobe of adult-onset hypothyroidism can be increased, which can be partly restored by T4 treatment in a small dose. There is obvious recuperation with a large dose of T4 treatment.