title: Effect of thyroxine on SNARE complex and synaptotagmin-1 expression in the prefrontal cortex of rats with adult-onset hypothyroidism.
abstract: Thyroid hormone insufficiency in adulthood causes a wide range of brain impairments, including altered synaptic proteins in the prefrontal cortex (PFC). The present study investigated whether adult-onset hypothyroidism altered the expression of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes and synaptotagmin-1 (syt-1) in the PFC of rats. Sprague-Dawley rats were randomly divided into 4 groups: control, hypothyroid, and hypothyroid treated with T(4) [5 or 20 μg/100 g body weight (BW)]. Adult-onset hypothyroidism was induced in rats with the antithyroid drug 6-n-propyl-2-thiouracil (ip injection). PFC levels of synaptosomal-associated protein of 25 kDa (SNAP-25), syntaxin-1, vesicle-associated membrane protein 2 (VAMP-2) and syt-1 were determined by immunohistochemistry and western blot analyses. The results showed that syntaxin-1 and syt-1 were expressed at significantly lower levels in hypothyroid rats, VAMP-2 levels were not altered, and SNAP-25 levels were much higher compared to controls. A 2-week treatment with 5 μg T(4)/100 g BW partially normalized levels of SNARE complex and syt-1, and 20 μg T(4)/100 g BW restored these proteins closer to normal levels. Our findings indicate that dysregulation of SNARE complex and syt-1 in PFC of adult-onset hypothyroidism can be restored by T(4) treatment.
authors.affiliation: Department of Endocrinology, Anhui Geriatric Institute, the First Affiliated Hospital of Anhui Medical University, Anhui, China.
authors.forename: H Y
authors.initials: HY
authors.lastname: Yang
authors.forename: C P
authors.initials: CP
authors.lastname: Sun
authors.forename: X M
authors.initials: XM
authors.lastname: Jia
authors.forename: L
authors.initials: L
authors.lastname: Gui
authors.forename: D F
authors.initials: DF
authors.lastname: Zhu
authors.forename: W Q
authors.initials: WQ
authors.lastname: Ma
mesh_terms: D000818:Animals; D001928:Brain Diseases, Metabolic / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D007037:Hypothyroidism / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050600:SNARE Proteins / Q000378:metabolism*; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D050863:Synaptotagmin I / Q000378:metabolism*; D050827:Syntaxin 1 / Q000378:metabolism; D013974:Thyroxine / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D014284:Triiodothyronine / Q000097:blood; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism
chemical_list: D050600:SNARE Proteins; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D050863:Synaptotagmin I; D050827:Syntaxin 1; C494312:Syt1 protein, rat; C494706:Vamp2 protein, rat; D050988:Vesicle-Associated Membrane Protein 2; D014284:Triiodothyronine; D013974:Thyroxine