Effect of thyroxine on munc-18 and syntaxin-1 expression in dorsal hippocampus of adult-onset hypothyroid rats.
Adult-onset hypothyroidism induces a variety of impairments on hippocampus-dependent neurocognitive functioningin which many synaptic proteins in hippocampus neurons are involved. Here, we observed the effect of adult-onset hypothyroidism on the expression of syntaxin-1 and munc-18 in the dorsal hippocampus and whether the altered proteins could be restored by levothyroxine (T4) treatment. All rats were separated into 4 groups randomly: hypothyroid group, 5 μg T4/100 g body weight (BW) treated group, 20 μg T4/100g BW treated group and control group. The radioimmunoassay kits were applied to assay the levels of serum T3 and T4, and the levels of syntaxin-1 and munc-18 in hippocampus were assessed by immunohistochemistry and Western blot. Both analysis corroborated that syntaxin-1 in the hypothyroid group was significantly higher. Munc-18 was lower in four layers of CA3 and dentate gyrus by immunohistochemistry. After two weeks of treatment with 5 μg T4/100g BW for hypothyroidism, syntaxin-1 levels were completely restored, whereas the recovery of munc-18 only located in two of the four impaired layers. Twenty μg T4/100g BW treatment normalized munc-18 levels. These data suggested that adult-onset hypothyroidism induced increment of syntaxin-1 and decrement of munc-18 in the dorsal hippocampus, which could be restored by T4 treatment. Larger dosage of T4 caused more effective restorations.
Department of Endocrinology, Anhui Geriatric Institute, the First Affiliated Hospital of Anhui Medical University, Hefei, China.
Y
Y
Zhu
D
D
Ning
F
F
Wang
C
C
Liu
Y
Y
Xu
X
X
Jia
D
D
Zhu
D000818:Animals; D018891:Dentate Gyrus / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D007037:Hypothyroidism / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051938:Munc18 Proteins / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050827:Syntaxin 1 / Q000096:biosynthesis*; D013974:Thyroxine / Q000494:pharmacology*
D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; D050827:Syntaxin 1; D013974:Thyroxine