Department of Neuroscience Feinberg School of Medicine, Weinberg College of Arts and Sciences, Northwestern University, Chicago, IL, USA.
Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Chicago, IL, USA.
Nat Neurosci. 2021 Dec;24(12):1648-1659. doi: 10.1038/s41593-021-00967-6. Epub 2021 Nov 29.
The mechanistic underpinnings of autism remain a subject of debate and controversy. Why do individuals with autism share an overlapping set of atypical behaviors and symptoms, despite having different genetic and environmental risk factors? A major challenge in developing new therapies for autism has been the inability to identify convergent neural phenotypes that could explain the common set of symptoms that result in the diagnosis. Although no striking macroscopic neuropathological changes have been identified in autism, there is growing evidence that inhibitory interneurons (INs) play an important role in its neural basis. In this Review, we evaluate and interpret this evidence, focusing on recent findings showing reduced density and activity of the parvalbumin class of INs. We discuss the need for additional studies that investigate how genes and the environment interact to change the developmental trajectory of INs, permanently altering their numbers, connectivity and circuit engagement.
自闭症的发病机制仍然是一个争论和争议的话题。为什么自闭症患者尽管具有不同的遗传和环境风险因素，但仍具有重叠的一系列非典型行为和症状？自闭症新疗法开发的主要挑战之一是无法识别趋同的神经表型，这些表型可以解释导致诊断的一系列常见症状。尽管在自闭症中没有发现明显的宏观神经病理学变化，但越来越多的证据表明抑制性中间神经元（IN）在其神经基础中发挥着重要作用。在这篇综述中，我们评估和解释了这方面的证据，重点是最近发现的 IN 中 parvalbumin 类的密度和活性降低的发现。我们讨论了需要进行更多的研究，以调查基因和环境如何相互作用改变 IN 的发育轨迹，从而永久改变它们的数量、连接性和回路参与。
