Mitochondrial Ferritin Deletion Exacerbatesβ-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 attenuatesβ-amyloid- and 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells. To explore the protective effects of FtMt onβ-amyloid-induced memory impairment and neuronal apoptosis and the mechanisms involved, 10-month-old wild-type andFtmtknockout mice were infused intracerebroventricularly (ICV) with Aβ25–35to establish an Alzheimer’s disease model. Knockout ofFtmtsignificantly exacerbated Aβ25–35-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 inFtmtknockout 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 inFtmtknockout mice treated with Aβ25–35. In conclusion, this study demonstrated that the neurological impairment induced by Aβ25–35was exacerbated inFtmtknockout mice and that this may relate to increased levels of oxidative stress.