首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Evaluation of neuroactive steroid levels by liquid chromatography-tandem mass spectrometry in central and peripheral nervous system: effect of diabetes.
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Evaluation of neuroactive steroid levels by liquid chromatography-tandem mass spectrometry in central and peripheral nervous system: effect of diabetes.

机译:通过液相色谱-串联质谱法评估中枢神经系统和周围神经系统的神经活性类固醇水平:糖尿病的影响。

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摘要

The nervous system is a target for physiological and protective effects of neuroactive steroids. Consequently, the assessment of their levels in nervous structures under physiological and pathological conditions is a top priority. To this aim, identification and quantification of pregnenolone (PREG), progesterone (PROG), dihydroprogesterone (DHP), tetrahydroprogesterone (THP), testosterone (T), dihydrotestosterone (DHT), 5alpha-androstan-3alpha, 17beta-diol (3alpha-diol), 17alpha- and 17beta-estradiol (17alpha-E and 17beta-E) by liquid chromatography and tandem mass spectrometry (LC-MS/MS) has been set up. After validation, this method was applied to determine the levels of neuroactive steroids in central (i.e., cerebral cortex, cerebellum and spinal cord) and peripheral (i.e., brachial nerve) nervous system of control and diabetic rats. In controls only the brachial nerve had detectable levels of all these neuroactive steroids. In contrast, 17alpha-E in cerebellum, 17alpha-E, 17beta-E, DHP and THP in cerebral cortex, and 17alpha-E, 17beta-E and DHP in spinal cord were under the detection limit. Diabetes, induced by injection with streptozotocin, strongly affected the levels of some neuroactive steroids. In particular, the levels of PREG, PROG and T in cerebellum, of PROG, T and 3alpha-diol in cerebral cortex, of PROG, DHT and 3alpha-diol in spinal cord and of PREG, DHP, THP, T, DHT and 3alpha-diol in brachial nerve were significantly decreased. In conclusion, the data here reported demonstrate that the LC-MS/MS method allows the assessment of neuroactive steroids in the nervous system with high sensitivity and specificity and that diabetes strongly affects their levels, providing a further basis for new therapeutic tools based on neuroactive steroids aimed at counteracting diabetic neuropathy.
机译:神经系统是神经活性类固醇的生理和保护作用的靶标。因此,在生理和病理条件下评估其在神经结构中的水平是当务之急。为此,对孕烯醇酮(PREG),孕酮(PROG),二氢孕酮(DHP),四氢孕酮(THP),睾丸激素(T),二氢睾丸酮(DHT),5alpha-雄甾烷3alpha,17beta-二醇(3alpha-已通过液相色谱和串联质谱(LC-MS / MS)建立了17α-雌二醇和17β-雌二醇(17α-E和17β-E)。验证后,该方法用于确定对照和糖尿病大鼠中枢神经系统(即大脑皮层,小脑和脊髓)和周围神经系统(即臂神经)中神经活性类固醇的水平。在对照中,仅臂神经具有所有这些神经活性类固醇的可检测水平。相反,小脑中的17alpha-E,大脑皮层中的17alpha-E,17beta-E,DHP和THP以及脊髓中的17alpha-E,17beta-E和DHP都在检测限以下。注射链脲佐菌素诱发的糖尿病强烈影响某些神经活性类固醇的水平。特别是小脑中的PREG,PROG和T,大脑皮层中的PROG,T和3α-二醇,脊髓中的PROG,DHT和3α-二醇以及PREG,DHP,THP,T,DHT和3alpha的水平臂神经中的α-二醇明显减少。总之,这里报道的数据表明,LC-MS / MS方法可以高度敏感和特异性地评估神经系统中的神经活性类固醇,并且糖尿病强烈影响其水平,为基于神经活性的新治疗工具提供了进一步的基础类固醇旨在抵抗糖尿病性神经病。

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