Ion mobility mass spectrometry provides novel insights into the expression and structure of gangliosides in the normal adult human hippocampus
Ion mobility mass spectrometry provides novel insights into the expression and structure of gangliosides in the normal adult human hippocampus
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DOI：
10.1039/c8an01118d
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发表时间：
2018-11-07
期刊：
影响因子：
4.2
通讯作者：
Zamfir, Alina D.
中科院分区：
文献类型：
--
作者：
Sarbu, Mirela;Vukelic, Zeljka;Zamfir, Alina D.
神经节苷脂（gangliosides，GG）是中枢神经系统（CNS）中的糖突触微区，参与功能性突触和神经回路的形成。因此，糖皮质激素是中枢神经系统疾病早期诊断的重要生物标志物，也是我们研究的重点，是潜在的治疗靶点。包括阿尔茨海默病和精神分裂症在内的一系列神经精神障碍的特征在于由海马萎缩和胆碱能活性降低引起的健忘症和定向障碍。基于离子迁移率质谱（IM-MS）的能力，可靠的测定glycopatastine，随着年龄的变化和神经系统疾病的发生的GG的多样性和数量的变化，我们在这里报告的发展，一个高性能的IM-MS战略评估GG的配置文件中提取的复杂的混合物从20岁的海马。基于电荷状态、糖链长度和唾液酸化程度的GG的IM分离导致了140种的检测和鉴定，这是有史以来在成人海马中报道的最大数量的GG。此外，所获得的数据支持GG胆碱能活性的概念。使用碰撞诱导解离（CID）的IM串联MS实验证实了研究的海马标本中GD1b（d18：1/24：1）的发生率。
Clustered into the so-called "glycosynaptic" microdomains in the central nervous system (CNS), gangliosides (GGs) are involved in the formation of functional synapses and neural circuits. Therefore, GGs are important biomarkers in the early diagnosis of CNS pathologies, which are the focus of our research as potential therapeutic targets. A series of neuropsychiatric disorders, including Alzheimer's disease and schizophrenia, are characterized by amnesia and disorientation caused by hippocampal atrophy and diminished cholinergic activity. Based on ion mobility mass spectrometry (IM-MS) capability for the reliable determination of glycopatterns, the changes in the diversity and number of GGs with age and the occurrence of neurological disorders, we report here the development of a high performance IM-MS strategy for assessing the GG profile in a complex mixture extracted from a 20 year old hippocampus. IM separation of GGs based on the charge state, carbohydrate chain length and degree of sialylation led to the detection and identification of 140 species, the largest number of GGs ever reported in an adult hippocampus. Moreover, the obtained data support the concept of GG cholinergic activity. IM tandem MS experiments using collision induced dissociation (CID) confirmed the incidence of GD1b(d18:1/24:1) in the investigated hippocampus specimen.