Characterization of peculiar behavioral phenotypes in animal models of neuroferritinopathies

Ferritin is the main intracellular iron storage protein, playing a central role in the regulation of iron metabolism and detoxification. Nucleotide insertions in the coding sequence of the ferritin light chain cause a neurodegenerative disease called neuroferritinopathy characterized by movement disorders. For this study we used a transgenic mouse model expressing the pathogenic mutant human ferritin light chain FTL498-499InsTC which we named Ln2. These transgenic mice showed some of the typical pathologic hallmarks of human neuroferritinopathy, including the accumulation of ferritin/iron bodies in the liver and brain and brain iron accumulation. Since biochemical and immunohistochemical analysis showed that the number and size of the ferritin/iron granules increased with age, we first aimed at characterizing behavioural abnormalities in LN2 old (21 months) mice treated twice a week for three weeks with two herbicides known to cause oxidative stress and neurodegeneration: Paraquat (PQ) and Maneb (MB). Experimental subjects were tested, at different times from treatment, for locomotor activity in a battery of test (Beam Walking, Climbing and Grip Strenght) and for exploratory activity in an Open Field test. While no major motor deficits emerged, 24 hours following the first treatment LN2 mice showed increased locomotor and exploratory activities compared to control subjects. These preliminary data suggest that brain iron accumulation together with oxidative stress in aged mice may result in a paradoxical behavioural activation.