Olfactory dysfunction is implicated in neurodegenerative disorders and typically manifests years before other symptoms. The cyanobacterial neurotoxin β-N-methylamino-L-alanine (BMAA) is suggested as a risk factor for neurodegenerative disease. Detection of BMAA in air filters has increased the concern that aerosolization may lead to human BMAA exposure through the air. The aim of this study was to determine if BMAA targets the olfactory system. Autoradiographic imaging showed a distinct localization of radioactivity in the right olfactory mucosa and bulb following a unilateral intranasal instillation of 3H-BMAA (0.018 µg) in mice, demonstrating a direct transfer of BMAA via the olfactory pathways to the brain circumventing the blood-brain barrier, which was confirmed by liquid scintillation. Treatment of mouse primary olfactory bulb cells with 100 µM BMAA for 24 h caused a disruption of the neurite network, formation of dendritic varicosities and reduced cell viability. The NMDA receptor antagonist MK-801 and the metabotropic glutamate receptor antagonist MCPG protected against the BMAA-induced alterations, demonstrating the importance of glutamatergic mechanisms. The ionotropic non-NMDA receptor antagonist CNQX prevented the BMAA-induced decrease of cell viability in mixed cultures containing both neuronal and glial cells, but not in cultures with neurons only, suggesting a role of neuron-glial interactions and glial AMPA receptors in the BMAA-induced toxicity. The results show that the olfactory region may be a target for BMAA following inhalation exposure. Further studies on the relations between environmental olfactory toxicants and neurodegenerative disorders are warranted.

中文翻译：

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蓝细菌神经毒素β-N-甲基氨基-L-丙氨酸（BMAA）靶向嗅球区域。

嗅觉功能障碍与神经退行性疾病有关，通常比其他症状早几年出现。蓝细菌神经毒素β-N-甲基氨基-L-丙氨酸（BMAA）被认为是神经退行性疾病的危险因素。空气滤清器中BMAA的检测增加了人们对雾化可能导致人体BMAA通过空气暴露的担忧。这项研究的目的是确定BMAA是否靶向嗅觉系统。放射自显影显示小鼠单侧鼻内滴注3H-BMAA（0.018 µg）后，右嗅粘膜和球囊中的放射性明显不同，这表明BMAA通过嗅觉途径直接转移至大脑，从而绕过了血脑屏障。 ，已通过液体闪烁确认。用100 µM BMAA处理小鼠原发性嗅球细胞24小时会导致神经突网络破裂，形成树突静脉曲张并降低细胞活力。NMDA受体拮抗剂MK-801和代谢型谷氨酸受体拮抗剂MCPG可以抵抗BMAA诱导的改变，从而证明了谷氨酸能机制的重要性。离子型非NMDA受体拮抗剂CNQX在含有神经元和神经胶质细胞的混合培养物中阻止了BMAA诱导的细胞活力的降低，但在仅具有神经元的培养物中却没有，提示神经元-神经胶质相互作用和神经胶质AMPA受体在BMAA中的作用诱导的毒性。结果表明，吸入暴露后，嗅觉区域可能是BMAA的靶标。