Departamento de Neurofarmacología, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City, Mexico.
J Neurosci Methods. 2011 Sep 30;201(1):35-45. doi: 10.1016/j.jneumeth.2011.07.009. Epub 2011 Jul 19.
Brain imaging and histopathological studies suggest that neurodevelopmental anomalies play a key role in the etiology of schizophrenia (SZ) and bipolar disorder (BD). New neuron formation and maturation occur in human olfactory epithelium throughout life. Therefore, the olfactory epithelium has been proposed as a model to study alterations in neurodevelopment, particularly in some psychiatric diseases. However, former studies were done with olfactory epithelium biopsies taken post mortem or under anesthesia from patients with SZ and BD. In this work we have developed a new method to obtain viable neural precursors by exfoliation of the anterior region of the medial lateral turbinate of the nasal cavity from healthy controls, and ambulatory patients. Cells were propagated to establish neural precursor banks. Thawed cells showed cytoskeletal phenotypes typical of developing neurons. They also conserved the ability to differentiate in presence of 2mM dibutyril-cyclic adenosine monophosphate, and maintained voltage-operated Ca(2+) currents in culture. Moreover, proportions of neuronal maturation stages were maintained in cultured exfoliates obtained from SZ and BD patients. Data support that neural precursors obtained from a nasal exfoliate are an excellent experimental model to later approach studies on biomarkers, neural development and cellular alterations in the pathophysiology of SZ and BD.
脑影像学和组织病理学研究表明,神经发育异常在精神分裂症(SZ)和双相情感障碍(BD)的病因学中起着关键作用。新神经元的形成和成熟发生在人类嗅上皮中,贯穿人的一生。因此,嗅上皮已被提议作为研究神经发育改变的模型,特别是在某些精神疾病中。然而,以前的研究是在 SZ 和 BD 患者死后或在麻醉下通过嗅上皮活检进行的。在这项工作中,我们开发了一种新的方法,通过从健康对照者和门诊患者的鼻腔中鼻甲的内侧面的前区域剥落来获得有活力的神经前体细胞。细胞被传代以建立神经前体细胞库。解冻的细胞表现出典型的发育神经元细胞骨架表型。它们还保留了在存在 2mM 丁二酰环腺苷单磷酸的情况下分化的能力,并在培养物中保持电压操作的 Ca(2+)电流。此外,在从 SZ 和 BD 患者获得的培养物中,神经成熟阶段的比例得到维持。数据支持从鼻上皮剥落获得的神经前体细胞是研究生物标志物、神经发育和 SZ 和 BD 病理生理学中细胞改变的绝佳实验模型。