Intraperitoneal injection of iron dextran induces peripheral iron overload and mild neurodegeneration in the nigrostriatal system in C57BL/6 mice

Elevated iron levels in the affected areas of brain are linked to several neurodegenerative diseases including Parkinson's disease (PD). This study investigated the influence of peripheral iron overload in peripheral tissues, as well as its entry into the brain regions on lysosomal functions. The survival of dopaminergic neurons in the nigrostriatal system and motor coordination were also investigated.An intraperitoneal injection of iron dextran (FeDx) mouse model was established. Western blot was used to detect iron deposition and lysosomal functions in the liver, spleen, hippocampal (HC), striatum (STR), substantia nigra (SN) and olfactory bulb (OB). Iron in serum and cerebrospinal fluid (CSF) was determined by an iron assay kit. Immunofluorescence and immunohistochemical staining were applied to detect dopaminergic neurons and fibers. Motor behavior was evaluated by gait analysis.Iron was deposited consistently in the liver and spleen, and serum iron was elevated. While iron deposition occurred late in the HC, STR and SN, without apparently affecting CSF iron levels. Although cathepsin B (CTSB), cathepsin D (CTSD), glucocerebrosidase (GCase) and lysosome integrated membrane protein 2 (LIMP-2) protein levels were dramatically up-regulated in the liver and spleen, they were almost unchanged in the brain regions. However, CTSB was up-regulated in acute iron-overloaded OB and primary cultured astrocytes. The number of dopaminergic neurons in the SN remained unchanged, and mice did not exhibit significant motor incoordination.Intraperitoneal injection of FeDx in mice induces largely peripheral iron overload while not necessarily sufficient to cause severe disruption of the nigrostriatal system.