Mitochondrial Ferritin Deletion Exacerbates <i>β</i>‐Amyloid‐Induced Neurotoxicity in Mice

Abstract

Mitochondrial ferritin (FtMt) is a mitochondrial iron storage protein which protects mitochondria from iron-induced oxidative damage. Our previous studies indicate that FtMt attenuates <i>β</i>-amyloid- and 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells. To explore the protective effects of FtMt on <i>β</i>-amyloid-induced memory impairment and neuronal apoptosis and the mechanisms involved, 10-month-old wild-type and <i>Ftmt</i> knockout mice were infused intracerebroventricularly (ICV) with A<i>β</i>_25-35 to establish an Alzheimer's disease model. Knockout of <i>Ftmt</i> significantly exacerbated A<i>β</i>_25-35-induced learning and memory impairment. The Bcl-2/Bax ratio in mouse hippocampi was decreased and the levels of cleaved caspase-3 and PARP were increased. The number of neuronal cells undergoing apoptosis in the hippocampus was also increased in <i>Ftmt</i> knockout mice. In addition, the levels of L-ferritin and FPN1 in the hippocampus were raised, and the expression of TfR1 was decreased. Increased MDA levels were also detected in <i>Ftmt</i> knockout mice treated with A<i>β</i>_25-35. In conclusion, this study demonstrated that the neurological impairment induced by A<i>β</i>_25-35 was exacerbated in <i>Ftmt</i> knockout mice and that this may relate to increased levels of oxidative stress.