کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5534703 1551267 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Novel spiroimidazopyridine derivative SAK3 improves methimazole-induced cognitive deficits in mice
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Novel spiroimidazopyridine derivative SAK3 improves methimazole-induced cognitive deficits in mice
چکیده انگلیسی


- We defined the mechanisms underlying cognitive impairment by methimazole-induced hypothyroidism.
- We developed the spiroimidazopyridine derivative SAK3 as cognitive enhancer.
- SAK3 treatment could antagonize methimazole-induced impairment in patients with hypothyroidism.

Methimazole (MMI) is a first-line therapy used to manage hyperthyroidism and Graves' disease. Despite its therapeutic benefit, chronic MMI administration can lead to hypothyroidism and perturb brain homeostasis in patients, resulting in neuropsychiatric disorders such as depression and cognitive dysfunction. We recently developed the spiroimidazopyridine derivative SAK3 as cognitive enhancer; however, mechanisms underlying its activity remained unclear. Here, we show that SAK3 potentially improves cognitive impairment seen following MMI-induced hypothyroidism. Twenty-four hours after MMI (75 mg/kg, i.p.) treatment, we administered SAK3 (0.1, 0.5 and 1 mg/kg, p.o.) to mice daily for 7 days. MMI treatment alone disrupted olfactory bulb (OB) glomerular structure, as assessed by staining with the olfactory marker protein (OMP), reduced the number of choline acetyl transferase (ChAT)-immunoreactive neurons in medial septum (MS), and significantly impaired cognition. SAK3 (0.5 and 1 mg/kg, p.o.) administration significantly restored the number of cholinergic MS neurons in MMI-treated mice, and SAK3 treatment at a higher dose significantly improved cognitive deficits seen in MMI-treated control mice. Overall, our study suggests that SAK3 treatment could antagonize such impairment in patients with hypothyroidism.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 108, September 2017, Pages 91-99
نویسندگان
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