医学期刊 Biological Psychiatry 最新发布的有关自闭症的文章表示：

“神经细胞中出现的与自闭症相关的差异表明，这些差异在生命的早期阶段就出现了。”

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自闭症是一种神经发育疾病，研究人员现在可以把原因追溯到产前发育，尽管这种疾病直到18个月以后才能被诊断出来。最近的一项研究表明，人类脑细胞的非典型发育始于大脑形成的最早期阶段，即单个脑细胞的阶段。

这项研究是由伦敦国王学院和英国剑桥大学的科学家进行的，论文发表在Elsevier出版的《生物精神病学》 （Biological Psychiatry） 杂志上。

监督这项研究的伦敦国王学院基础和临床神经科学系的MRC神经发育障碍中心的Deepak Srivastava博士说:“在这项研究中，我们使用诱导多能干细胞(iPSCs)来模拟早期大脑发育。 我们的发现表明，自闭症患者的脑细胞发育不同于普通人（typical individuals）。 ”

研究人员从9名自闭症患者和6名普通人中分离出头发样本。通过使用一系列生长因子处理细胞，科学家们得以驱动毛发细胞成为神经细胞或神经元——很像在大脑皮层或中脑区域发现的那些细胞。iPSCs保留了它们来自人的遗传特征，细胞重新开始发育，就像在子宫里发生的那样，这为观察人们的大脑发育提供了一个“窗口”。

剑桥自闭症研究中心和伦敦国王学院基础和临床神经科学系的分子生物学家Dwaipayan Adhya博士说:“使用来自头发样本的iPSCs，是研究自闭症患者早期大脑发育的最道德的方法。它绕过了动物研究的阶段，它是非侵入性的，它只需要一根头发或皮肤样本。”

在不同的阶段，作者检查了发育中细胞的外观，并对它们的RNA进行了测序，以观察细胞表达的是哪些基因。

在第9天，普通人的发育神经元形成“神经玫瑰花结”（neural rosettes），这是一种精巧的蒲公英形状，是典型的发育神经元。自闭症患者的细胞形成较小的玫瑰花结，或根本不形成玫瑰花结。自闭症患者的关键发育基因在细胞中的表达水平较低。

在第21天和第35天，普通人和自闭症患者的细胞在许多方面都有显著差异。这表明大脑皮层神经元的组成在自闭症患者与普通人的大脑发育中存在差异。

《生物精神病学》主编John Krystal博士在谈到这一发现时说： “神经细胞中出现的与自闭症相关的差异表明，这些差异在生命的早期阶段就出现了。”

与大脑皮层神经元中看到的差异不同，定向发育为“中脑神经元”的细胞(一个与自闭症功能障碍无关的大脑区域)在普通人和自闭症患者之间仅显示出可忽略不计的差异。

“iPSCs的使用使我们能够更精确地体查自闭症和普通人神经细胞中发生的基因演变与细胞命运的差异。Srivastava博士说:“这些有助于我们理解大脑发育的多样性。”

剑桥自闭症研究中心主任SimonBaron-Cohen博士是这项研究的共同负责人，他补充说:“有些人可能会担心，对自闭症患者和普通新生儿大脑差异的基础研究可能旨在‘预防’、‘根除’或‘治愈’自闭症。这不是我们的动机，我们在反对优生学和重视神经多样性的价值观上直言不讳。这类研究目的将使我们 更好地理解自闭症和普通人的大脑发育。 ”

“大脑是科学研究中的终极黑匣子。在这里，研究者使用了从外周干细胞衍生的神经细胞来窥视这个黑匣子的内部。这项重要的研究表明——我们可以了解更多大脑发育中的奥秘，并且正在加深我们对自闭症的理解。”Krystal博士最后说。

（以下为英文原文报道）

Autistic people's nerve cells

differ before birth

Researchers report differences in the autistic brain are

seen at the earliest stage of development

Autism is a neurodevelopmental condition that researchers are now tracing back to prenatal development, even though the disorder is not diagnosed until at least 18 months of age. A new study now shows in human brain cells that the atypical development starts at the very earliest stages of brain organization, at the level of individual brain cells.

The study from scientists at King's College London and Cambridge University, UK appears in Biological Psychiatry, published by Elsevier.

Deepak Srivastava, PhD, from the MRC Centre for Neurodevelopmental Disorders and Department of Basic and Clinical Neuroscience at King's College London, who supervised the study, said: "In this study we used induced pluripotent stem cells, or iPSCs, to model early brain development. Our findings indicate that brain cells from autistic people develop differently to those from typical individuals."

The researchers isolated hair samples from nine autistic people and six typical people. By treating the cells with an array of growth factors, the scientists were able to drive the hair cells to become nerve cells, or neurons -- much like those found in either the cortex or the midbrain region. iPSCs retain the genetic identity of the person from which they came and the cells re-start their development as it would have happened in the womb, providing a window into that person's brain development.

Dwaipayan Adhya, PhD, a molecular biologist at the Autism Research Centre in Cambridge and Department of Basicand Clinical Neuroscience at King's College London, said: "Using iPSCs from hair samples is the most ethical way to study early brain development inautistic people. It bypasses the need for animal research, it is non-invasive and it simply requires a single hair or skin sample from a person."

At various stages, the authors examined the developing cells' appearance and sequenced their RNA, to see which genes the cells were expressing.

At day 9, developing neurons from typical people formed "neural rosettes," an intricate, dandelion-like shape indicative of typically developing neurons. Cells from autistic people formed smaller rosettes or did not form rosettes at all. And key developmental genes were expressed at lower levels in cells from autistic people.

At days 21 and 35, the cells from typical and autistic people differed significantly in a number of ways, suggesting that the makeup of neurons in the cortex differs in the autistic and typically developing brain.

John Krystal, PhD, Editor-in-Chief of Biological Psychiatry, said of the findings: "The emergence of differences associated with autism in these nerve cells shows that these differences arise very early in life."

In contrast to the differences seen in cortical neurons, cells directed to develop as midbrain neurons -- a brain region not implicated in autism dysfunction -- showed only negligible differences between typical and autistic people.

"The use of iPSCs allows us to examine more precisely the differences in cell fates and gene pathways that occur in neural cells from autistic and typical individuals. These findings will hopefully contribute to our understanding of why there is such diversity in brain development," said Dr. Srivastava.

Simon Baron-Cohen, PhD, Director of the Autism Research Centre at Cambridge, who co-led the study, added,"Some people may be worried that basic research into differences in the autistic and typical brain prenatally may be intended to 'prevent,''eradicate,' or 'cure' autism. This is not our motivation, and we are outspoken in our values in standing up against eugenics and in valuing neurodiversity.Such studies will lead to a better understanding of brain development in both autistic and typical individuals."

"The brain has been the ultimate black box. Here, the authors have used nerve cells derived from peripheral stem cells to peek inside this box. This important study suggests that this is possible and is deepening our understanding of autism," Dr. Krystal added.

新闻来源: Elsevier. "Autistic people's nerve cells differ before birth: Researchers report differences in theautistic brain are seen at the earliest stage of development."ScienceDaily. ScienceDaily, 24 August 2020.

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