Department of Pharmacodynamics, Semmelweis University, 4 Nagyvárad tér, H-1089 Budapest, Hungary.
Int J Mol Sci. 2022 Aug 21;23(16):9460. doi: 10.3390/ijms23169460.
Gangliosides are glycosphingolipids of the plasma membrane and are highly enriched in the nervous system where they play a vital role in normal cell functions. Furthermore, several studies suggest their potential involvement in the pathogenesis of neurological conditions. Since cyclodextrins (CDs) can form inclusion complexes with various lipids, methylated beta-CDs are widely used in biomedical research to extract cholesterol from the membrane and study its cellular role. Despite CDs being known to interact with other membrane lipid components, their effect on gangliosides is poorly characterized. The aim of this research was to investigate the effect of dimethyl-beta-cyclodextrin (DIMEB), hydroxypropyl-beta-cyclodextrin (HPBCD), randomly methylated-alpha-cyclodextrin (RAMEA), and hydroxypropyl-alpha-cyclodextrin (HPACD) on ganglioside and cholesterol levels in rat brain synaptosomes. Their effect on membrane integrity and viability was also assessed. We examined the role of lipid depletion by CDs on the release of the major excitatory neurotransmitter, glutamate. Selective concentration range for cholesterol depletion was only found with HPBCD, but not with DIMEB. Selective depletion of gangliosides was achieved by both RAMEA and HPACD. The inhibition of stimulated glutamate release upon ganglioside depletion was found, suggesting their potential role in neurotransmission. Our study highlights the importance of the characterization of the lipid depleting capability of different CDs.
神经节苷脂是质膜糖脂，在神经系统中高度富集，在正常细胞功能中发挥着重要作用。此外，几项研究表明它们可能参与了神经疾病的发病机制。由于环糊精（CDs）可以与各种脂质形成包合物，因此甲基-β-CD 广泛用于生物医学研究，以从膜中提取胆固醇并研究其细胞作用。尽管已知 CDs 与其他膜脂质成分相互作用，但它们对神经节苷脂的影响尚未得到很好的描述。本研究旨在研究二甲基-β-环糊精（DIMEB）、羟丙基-β-环糊精（HPBCD）、随机甲基-α-环糊精（RAMEA）和羟丙基-α-环糊精（HPACD）对大鼠脑突触体中神经节苷脂和胆固醇水平的影响。还评估了它们对膜完整性和活力的影响。我们研究了 CDs 对脂质耗竭对主要兴奋性神经递质谷氨酸释放的影响。仅在 HPBCD 中发现了胆固醇耗竭的选择性浓度范围，而在 DIMEB 中未发现。RAMEA 和 HPACD 均可选择性耗尽神经节苷脂。发现神经节苷脂耗竭后刺激的谷氨酸释放受到抑制，这表明它们在神经传递中可能具有作用。我们的研究强调了表征不同 CDs 的脂质耗竭能力的重要性。
