Harmful algal blooms (HABs) produce neurotoxins that affect human health. Developmental exposure of zebrafish embryos to the HAB toxin domoic acid (DomA) causes myelin defects, loss of reticulospinal neurons, and behavioral deficits. However, it is unclear whether DomA primarily targets myelin sheaths, leading to the loss of reticulospinal neurons, or reticulospinal neurons, causing myelin defects. Here, we show that while exposure to DomA at 2 dpf did not reduce the number of oligodendrocyte precursors prior to myelination, it led to fewer myelinating oligodendrocytes that produced shorter myelin sheaths and aberrantly wrapped neuron cell bodies. DomA-exposed larvae lacked Mauthner neurons prior to the onset of myelination, suggesting that axonal loss is not secondary to myelin defects. The loss of the axonal targets may have led oligodendrocytes to inappropriately myelinate neuronal cell bodies. Consistent with this, GANT61, which reduces oligodendrocyte number, caused a reduction in aberrantly myelinated neuron cell bodies in DomA-exposed fish. Together, these results suggest that DomA initially alters reticulospinal neurons and the loss of axons causes aberrant myelination of nearby cell bodies. The identification of initial targets and perturbed cellular processes provides a mechanistic understanding of how DomA alters neurodevelopment, leading to structural and behavioral phenotypes.

中文翻译：

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发育性暴露于软骨藻酸靶向网状脊髓神经元并导致脊髓中的异常髓鞘形成

有害藻华 (HAB) 会产生影响人类健康的神经毒素。斑马鱼胚胎发育暴露于 HAB 毒素软骨藻酸 (DomA) 会导致髓鞘缺陷、网状脊髓神经元丧失和行为缺陷。然而，尚不清楚 DomA 是否主要针对髓鞘，导致网状脊髓神经元或网状脊髓神经元丢失，导致髓鞘缺陷。在这里，我们表明，虽然暴露于 2 dpf 的 DomA 并没有减少髓鞘形成前少突胶质细胞前体的数量，但它导致产生较短髓鞘和异常包裹的神经元细胞体的髓鞘形成少突胶质细胞减少。暴露于 DomA 的幼虫在髓鞘形成之前缺乏 Mauthner 神经元，这表明轴突损失不是继发于髓鞘缺陷。轴突靶标的丢失可能导致少突胶质细胞不适当地形成髓鞘神经元细胞体。与此一致，减少少突胶质细胞数量的 GANT61 导致暴露于 DomA 的鱼中异常有髓神经元细胞体的减少。总之，这些结果表明 DomA 最初会改变网状脊髓神经元，而轴突的缺失会导致附近细胞体的异常髓鞘形成。对初始目标和受干扰的细胞过程的识别提供了对 DomA 如何改变神经发育、导致结构和行为表型的机械理解。这些结果表明，DomA 最初会改变网状脊髓神经元，而轴突的缺失会导致附近细胞体的异常髓鞘形成。对初始目标和受干扰的细胞过程的识别提供了对 DomA 如何改变神经发育、导致结构和行为表型的机械理解。这些结果表明，DomA 最初会改变网状脊髓神经元，而轴突的缺失会导致附近细胞体的异常髓鞘形成。对初始目标和受干扰的细胞过程的识别提供了对 DomA 如何改变神经发育、导致结构和行为表型的机械理解。