Role of Ferric Citrate on Neuronal Cell functions and detection of the iron via radiation fluorescence and magnetic signal change

Abstract

Iron is not only crucial for brain function, but also accelerates brain degeneration and cognitive decline. Various forms of iron exist in the human body, including small molecule iron, also known as non-transferrin-bound or labile iron, present in both normal and excessive iron conditions. Recent studies suggest a potential link between labile iron and the development of neurodegenerative disorders, although the comprehensive role of labile iron remains incompletely understood. This research, including in vitro, in vivo, and iron imaging approaches, aims to investigate how labile iron influences neuronal cell function and its interaction with lysosomal functions. High-resolution imaging tools, including confocal Tau-Sted microscopy, Synchrotron Radiation X-ray fluorescence (XRF) nanoscopy, and Magnetic Resonance Imaging (MRI), were employed to visualize labile iron. Results indicate that labile iron is involved in lysosomal clearance function, leading to protein aggregation and abnormal autophagy processes, but this alteration can be reversed either by introducing fresh media or utilizing an iron chelator in an in vitro model. Likewise, analysis at the molecular level in an in vivo model uncovers the impacts of an iron rich diet in rats, such as apoptosis, autophagy process, and the accumulation of protein aggregation. However, the neuronal activities both in vitro and in vivo models are increased in synapse function. Moreover, the developed Tau-STED technique and Synchrotron Radiation XRF nanoscopy successfully observed labile iron in primary hippocampal neurons, revealing its transport within lysosomes through dendrites and axons, leading to propose the concept of labile iron transporting in lysosomes through dendrites and axons. Notably, MRI imaging demonstrated an increased signal when employing a tannic acid (TA) as an iron chelator, which might pave the way to develop the standard scanning method for labile iron imaging. Collectively, the studies emphasize the crucial role of preserving labile iron in neuronal cells, hinting at potential therapeutic implications for manipulating labile iron dynamics to address neurodegenerative processes in the future.