Related Experiment Video
Updated: Jul 10, 2026
Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
Mitochondrial Ferritin Deletion Exacerbates β-Amyloid-Induced Neurotoxicity in Mice
Peina Wang1, Qiong Wu1, Wenyue Wu1
1Laboratory of Molecular Iron Metabolism, The Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang, Hebei 050024, China.
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 β-amyloid- and 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells. To explore the protective effects of FtMt on β-amyloid-induced memory impairment and neuronal apoptosis and the mechanisms involved, 10-month-old wild-type and Ftmt knockout mice were infused intracerebroventricularly (ICV) with Aβ25-35 to establish an Alzheimer's disease model. Knockout of Ftmt significantly 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 in Ftmt 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 Ftmt knockout mice treated with Aβ25-35. In conclusion, this study demonstrated that the neurological impairment induced by Aβ25-35 was exacerbated in Ftmt knockout mice and that this may relate to increased levels of oxidative stress.
Insights
Mitochondrial ferritin (FtMt) deficiency worsens Alzheimer's-like memory loss and brain cell death caused by amyloid beta. This suggests FtMt protects against neurodegeneration and oxidative stress in the brain.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Mitochondrial ferritin (FtMt) is a key protein for managing iron within mitochondria, protecting cells from oxidative damage.
- Previous research shows FtMt can protect against neurotoxic agents like beta-amyloid (Aβ) in cell cultures.
Purpose of the Study:
- To investigate the protective role of FtMt against Aβ-induced memory deficits and neuronal apoptosis in a mouse model.
- To elucidate the underlying molecular mechanisms, focusing on oxidative stress and cell death pathways.
Main Methods:
- An Alzheimer's disease model was created in 10-month-old wild-type and Ftmt knockout mice via intracerebroventricular infusion of Aβ25-35.
- Evaluated learning and memory, hippocampal apoptosis markers (Bcl-2/Bax ratio, cleaved caspase-3, PARP), oxidative stress (MDA), and iron-related proteins (L-ferritin, FPN1, TfR1).
Main Results:
- Ftmt knockout mice exhibited significantly worsened Aβ25-35-induced learning and memory impairment.
- Apoptosis markers were elevated, and neuronal apoptosis increased in the hippocampus of Ftmt knockout mice.
- Increased oxidative stress (MDA) and altered iron metabolism markers were observed in Ftmt knockout mice.
Conclusions:
- Neurological impairment from Aβ25-35 is exacerbated by the absence of mitochondrial ferritin.
- FtMt deficiency appears to increase susceptibility to Aβ-induced neurotoxicity, likely through enhanced oxidative stress.
