Systematic expression of immediate early genes and intensive astrocyte activation induced by intrastriatal ferrous iron injection.

The potential role(s) of transitional metals such as iron have been implicated in neurodegeneration through biochemical processes, particularly oxidative stress. We injected ferrous chloride (FeCl2) and ferric chloride (FeCl3) into the striatonigral system of Sprague-Dawley rats to investigate the biological and toxic effects of ferrous iron in the central nervous system. When FeCl2 was injected into the ventral midbrain, rats showed a characteristic behavior which indicated ipsilateral dopaminergic hyperactivity. FeCl2 injection into the striatum induced a dose-dependent damage, the activation of astrocytes and recruitment of macrophage/microglia at the injected site. Interestingly, the activation of astrocytes was also observed in the anatomically remote areas such as the ipsilateral subthalamic nucleus and pars reticulata of the substantia nigra after 1 week. Expression of immediate early genes (IEGs; c-fos and NGFI-A) was observed in the cortex, thalamic nuclei, subthalamic nucleus, pars reticulata of the substantia nigra, lateral and medial geniculate bodies on the ipsilateral side from 3 to 15 h after FeCl2 injection. Pre-treatment with dimethyl sulfoxide, a hydroxyl radical scavenger, prevented FeCl2-induced expression of IEGs in the thalamic nuclei and geniculate bodies, but not in the cerebral cortex. On the other hand, the effects of FeCl3 were faint and limited on IEGs expression and tissue damage. These results suggest that ferrous iron affects the nervous system vigorously, possibly yielding free radicals such as hydroxyl radicals, and could be one of the important candidates for neurodegenerative diseases under the state in which acclimating systems for iron toxicity are disrupted.