Tox Path Specialists, LLC, A StageBio Company, Frederick, MD, USA.
Genentech, Inc, South San Francisco, CA, USA.
Toxicol Pathol. 2020 Jan;48(1):238-243. doi: 10.1177/0192623319857053. Epub 2019 Jul 3.
Although necrosis and apoptosis are uncommon, autophagy of sensory neurons (ASN) in trigeminal and dorsal root ganglia is a very common, spontaneous finding in cynomolgus monkeys (). Data from one author's (Butt) laboratory showed 12 of 22 studies (year range 2017 to 2019) that included the evaluation of sensory ganglia from cynomolgus monkeys had at least one control animal with ASN. Autophagy of sensory neurons is characterized by a distinct cell membrane, cytoplasm filled with autolysosomes, disintegrated nuclear membrane, and/or globules of degraded chromatin. Since these changes are consistent with autophagy and indicate an irreversible state, a diagnosis of autophagy is preferred instead of necrosis or degeneration. Sensory ganglia are not commonly evaluated in nonclinical toxicology investigations so many pathologists may be unaware of this common change. Especially due to the typically small group size of monkey studies, the observation of this change in sensory ganglia may lead to a faulty interpretation that this change is due to the test article. This article describes the light microscopic and ultrastructural characteristics of neuronal autophagy in trigeminal and dorsal root ganglia and provides historical control data of the incidence of this change in cynomolgus monkeys.
尽管坏死和凋亡并不常见,但三叉神经和脊神经根节感觉神经元的自噬(ASN)是食蟹猴中非常常见的自发性发现()。一位作者(Butt)实验室的数据显示,在 2017 年至 2019 年期间进行的 22 项研究中有 12 项研究()包括对食蟹猴感觉神经节的评估,其中至少有 1 只对照动物存在 ASN。感觉神经元的自噬的特征是细胞膜明显,细胞质充满自噬体,核膜解体和/或降解染色质的小球。由于这些变化与自噬一致,并表明是不可逆状态,因此更倾向于诊断为自噬,而不是坏死或变性。感觉神经节在非临床毒理学研究中通常不进行评估,因此许多病理学家可能不知道这种常见变化。特别是由于猴子研究的典型小组规模较小,观察到这种感觉神经节的变化可能会导致错误的解释,认为这种变化是由于测试物质引起的。本文描述了三叉神经和脊神经根节神经元自噬的光镜和超微结构特征,并提供了食蟹猴中这种变化发生率的历史对照数据。