School of Nutritional Sciences and Wellness, The University of Arizona, Tucson, AZ 85721, USA.
Int J Mol Sci. 2024 Sep 26;25(19):10342. doi: 10.3390/ijms251910342.
Manganese (Mn) is an essential trace mineral for brain function, but excessive accumulation can cause irreversible nervous system damage, highlighting the need for proper Mn balance. ZIP14, ZnT10, and ZIP8 are key transporters involved in maintaining Mn homeostasis, particularly in the absorption and excretion of Mn in the intestine and liver. However, their roles in the brain are less understood. The blood-cerebrospinal fluid barrier and the blood-brain barrier, formed by the choroid plexus and brain blood vessels, respectively, are critical for brain protection and brain metal homeostasis. This study identified ZIP14 on the choroid plexus epithelium, and ZIP8 and ZnT10 in brain microvascular tissue. We show that despite significant Mn accumulation in the CSF of knockout mice, ZIP14 expression levels in the blood-cerebrospinal fluid barrier remain unchanged, indicating that ZIP14 does not have a compensatory mechanism for regulating Mn uptake in the brain in vivo. Additionally, Mn still enters the CSF without ZIP14 when systemic levels rise. This indicates that alternative transport mechanisms or compensatory pathways ensure Mn balance in the CSF, shedding light on potential strategies for managing Mn-related disorders.
锰 (Mn) 是大脑功能所必需的痕量矿物质，但过量积累会导致神经系统不可逆转的损伤，这凸显了维持适当 Mn 平衡的必要性。ZIP14、ZnT10 和 ZIP8 是参与维持 Mn 体内平衡的关键转运体，特别是在肠道和肝脏中 Mn 的吸收和排泄方面。然而，它们在大脑中的作用还不太清楚。血脑屏障和血脑脊液屏障分别由脉络丛和脑血管形成，对于大脑保护和脑内金属平衡至关重要。本研究鉴定了脉络丛上皮上的 ZIP14，以及脑微血管组织中的 ZIP8 和 ZnT10。我们表明，尽管 敲除小鼠的 CSF 中 Mn 积累显著，但血脑屏障中的 ZIP14 表达水平保持不变，这表明 ZIP14 没有体内调节脑内 Mn 摄取的代偿机制。此外，当全身水平升高时，Mn 仍会进入 CSF 而没有 ZIP14。这表明替代转运机制或代偿途径确保了 CSF 中的 Mn 平衡，为管理与 Mn 相关的疾病提供了潜在策略。
