Domoic acid (DA) is a neurotoxin produced during harmful algal blooms that accumulates in marine organisms that serve as food resources for humans. While acute DA neurotoxicity can cause seizures and hippocampal lesions, less is known regarding how chronic, subacute DA exposure in adulthood impacts the hippocampus. With more frequent occurrences of harmful algal blooms, it is important to understand the potential impact of repeated, low-level DA exposure on human health. To model repeated, low-dose DA exposure, adult mice received a single low-dose (0.75 ± 0.05 μg/g) of DA or vehicle weekly for 22 consecutive weeks. Quantitative immunohistochemistry was performed to assess the effects of repeated, low-level DA exposure on hippocampal cells and synapses. Vesicular glutamate transporter 1 (VGluT1) immunoreactivity within excitatory boutons in CA1 of DA-exposed mice was increased. Levels of other vesicular transporter proteins (i.e., VGluT2 and the vesicular GABA transporter (VGAT)) within boutons, and corresponding bouton densities, were not significantly altered in CA1, CA3, or dentate gyrus. There were no significant changes in neuron density or glial fibrillary acidic protein (GFAP) immunoreactivity following chronic, low-dose exposure. This suggests that repeated low doses of DA, unlike high doses of DA, do not cause neuronal loss or astrocyte activation in hippocampus in adult mice. Instead, these findings demonstrate that repeated exposure to low levels of DA leads to subtle changes in VGluT1 expression within CA1 excitatory boutons, which may alter glutamatergic transmission in CA1 and disrupt behaviors dependent on spatial memory.

软骨藻酸 (DA) 是有害藻类大量繁殖时产生的一种神经毒素，会在作为人类食物来源的海洋生物体内积累。虽然急性 DA 神经毒性可导致癫痫发作和海马损伤，但对于成年期慢性、亚急性 DA 暴露如何影响海马体，人们知之甚少。随着有害藻华的发生越来越频繁，了解反复接触低水平 DA 对人类健康的潜在影响非常重要。为了模拟重复的低剂量 DA 暴露，成年小鼠每周接受一次低剂量 (0.75 ± 0.05 μg/g) DA 或媒介物，连续 22 周。进行定量免疫组织化学以评估重复、低水平 DA 暴露对海马细胞和突触的影响。暴露于 DA 的小鼠 CA1 区兴奋性波顿内的囊泡谷氨酸转运蛋白 1 (VGluT1) 免疫反应性增加。布顿内其他囊泡转运蛋白(即VGluT2和囊泡GABA转运蛋白(VGAT))的水平以及相应的布顿密度在CA1、CA3或齿状回中没有显着改变。长期、低剂量暴露后，神经元密度或胶质纤维酸性蛋白（GFAP）免疫反应性没有显着变化。这表明，与高剂量 DA 不同，重复低剂量 DA 不会导致成年小鼠海马神经元丢失或星形胶质细胞激活。相反，这些发现表明，反复暴露于低水平的 DA 会导致 CA1 兴奋性开关内 VGluT1 表达的微妙变化，这可能会改变 CA1 中的谷氨酸传递并扰乱依赖于空间记忆的行为。