| ObjectiveTo evaluate the thyroxin and donepezil (DON) effcct on the expression levels of thesynaptic proteins syntaxin-1and munc-18, as well as the content of the neurotransmitteracetylcholine (ACh) in the hippocampus of adult hypothyroid rats and clarify thepossible mechanism under the hypothyroidism-induced cognitive dysfunction.Methods55Sprague-Dawley rats were randomly divided into five groups: control, hypothyroid(PTU:0.05%; added to the drinking water), hypothyroid treated with T4(6μg/100gbody weight once daily; ip injection), hypothyroid treated with DON (0.005%; added tothe drinking water) and a combination of both drugs (T4:6μg/100g; DON:0.005%).The the levels of serum T3, T4and TSH were measured by radioimmunoassay kits.Concentration of Ach was determined in the homogenated hippocampus of each animaland the modified method of Hestrin was applied to assay Ach content. Protein levels ofsyntaxin-1and munc-18were determined by immunohistochemistry.Results1.Body weight gain：There were no group differences in the body weight of the rats atthe beginning of the research（P＞0.05）. After modeling, the respective increase ofbody weight in the control group, Hypo group, DON group, T4group andco-administration group was49.5%,21.3%,19.7%,31.7%and32.1%. Comparing tothe controls, the body weights of the rats in other groups were significantly lighter (P <0.05). 2. The levels of thyroid hormones：Comparing to the controls, serum T3and T4levelswere significantly lower (P <0.05) while TSH levels were higher (P <0.01) in thehypothyroid group, and the T3, T4and TSH levels were restored in the T4group(P>0.05).3.The expression levels of syntaxin-1and munc-18: In the hippocampus of thehypothyroid group, syntaxin-1was expressed at significantly higher levels (P <0.01),while the expression levels of munc-18were decreased compared with the levels in thecontrol group (P <0.01). Treatment with T4alone restored the expression of syntaxin-1but failed to normalize munc-18expression levels. The co-administration of T4andDON returned the munc-18levels to normal values.4.The content of Ach: In the hippocampus of the hypothyroid rats, Ach content wassignificantly decreased compared with that in the controls (P <0.05), both T4monotherapy and DON administration restored the ACh content to normal values.Conclusion1, Adult-onset hypothyroidism induces alterations in the levels of munc-18, syntaxin-1expression and ACh content in the hippocampus.2, Syntaxin-1and ACh levels were restored by T4monotherapy while munc-18levelswere not. In addition, the co-administration of T4and DON resulted in more effectiverestoration than either alone. |
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