Effect of thyroxine on SNARE complex and synaptotagmin-1 expression in the prefrontal cortex of rats with adult-onset hypothyroidism.

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.