DECIPHERING THE ORIGIN OF MAGNETITE IN HUMAN BRAIN TISSUE

来自几个门的动物被认为能探测到磁场并利用它来为自己服务。最引人注目的例子来自于趋磁细菌，它们含有单畴（约40-200纳米）磁铁矿（Fe3O4）或灰长铁矿（Fe3S4）晶体，称为磁小体。磁小体固定在细胞内，迫使细菌沿着磁力线游动。有趣的是，人脑组织中含有的磁铁矿晶体与某些趋磁细菌中发现的晶体具有相同的形态。我们之前的工作表明，在7个解剖的、完整的死后人类大脑中，有系统的单畴磁铁矿分布，这表明人体内部生物矿化氧化铁。其他研究报道了人类脑组织中更小的（< 40 nm，超顺磁性）磁铁矿，并表明超顺磁性磁铁矿来自外部来源。该提案旨在确定人类大脑中单畴和超顺磁性磁铁矿颗粒的性质，浓度和来源。我们希望进一步测试福尔马林固定组织和新鲜冷冻组织之间的磁性特征是否存在差异。我们建议应用独特的磁性方法来绘制磁铁矿的相对晶粒尺寸和化学成分，以及确定磁铁矿晶体在人脑中的空间取向（各向异性）。磁铁矿粒度、磁铁矿化学和/或几何结构（各向异性）的系统分布将构成确定人脑中磁铁矿起源的开创性证据。如果磁铁矿确实被证明具有生物起源，那么在随后的研究中了解它的功能应该会导致人类大脑研究的重要进展。如果是环境，那么了解颗粒如何进入并储存在大脑中，以及它们在生理条件下的反应性，同样将对未来的研究产生巨大影响。

Animals from several phyla are thought to detect the magnetic field and use it to their advantage. The most compelling example comes from magnetotactic bacteria that contain single domain (ca. 40-200 nm) magnetite (Fe3O4) or greigite (Fe3S4) crystals, called magnetosomes. Magnetosomes are fixed within the cell that compel the bacteria to swim along magnetic field lines. Interestingly, human brain tissue contains magnetite crystals that have identical morphologies as those found in some magnetotactic bacteria. Our previous work showed a systematic distribution of single domain magnetite in seven dissected, entire post mortem human brains suggesting the body internally biomineralizes the iron oxide. Other studies have reported much smaller (< 40 nm, superparamagnetic) magnetite in human brain tissue and suggested the superparamagnetic magnetite originates from external sources. This proposal aims to determine the properties, concentrations and the origin of both single domain and superparamagnetic magnetite particles in the human brain. We wish to further test whether a difference exists in magnetic characteristics between formalin-fixed tissue and fresh-frozen tissue. We propose to apply unique magnetic methods that will map the relative grain size and chemical composition of the magnetite as well as determine the spatial orientation (anisotropy) of the magnetite crystals in human brains. Systematic distribution in magnetite grain size, magnetite chemistry and/or geometric construction (anisotropy) would constitute groundbreaking evidence to determine the origin of magnetite in the human brain. If the magnetite is indeed shown to have a biogenic origin, then understanding its function in subsequent research should lead to important advances in human brain studies. If environmental, then understanding how the particles enter and become stored in the brain and their reactivity in physiological conditions will likewise have a huge impact on future research.