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Assessing Iron Deposition in the Brains of 5xFAD Mice by Perls'/DAB Staining
Published on: May 23, 2025
The protective effect of lactoferrin on ventral mesencephalon neurons against MPP + is not connected with its iron
Jun Wang1, Mingxia Bi1, Huiying Liu2
1Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao 266071, China.
Abstract:
Lactoferrin (Lf) can bind to lactoferrin receptor (LfR), leading to iron transport through the plasma membrane. Besides iron transportation, Lf also has antioxidant and anti-inflammatory properties. In the brain, Lf is only synthesized by activated microglia. LfR is present in blood vessels and nigral dopaminergic neurons. Both nigral iron accumulation and microglia activation is believed to be involved in Parkinson's disease (PD), moreover, increased Lf and LfR in dopaminergic neurons were found in PD cases and MPTP-intoxicated mice. How iron influences microglia to release Lf? Does Lf tend to transport iron to dopaminergic neurons leading to cell death or to protect dopaminergic neuron from neurotoxin? In this study, we observed that iron increased Lf synthesis in activated microglia. In ventral mesencephalon neurons, both iron-free Lf (apo-Lf) and iron-saturated Lf (holo-Lf) exerted neuroprotective effects against MPP(+) by mechanisms, believed to enhance the mitochondrial transmembrane potential, improve Cu/Zn-superoxide dismutase activity, increase Bcl-2 expression. Although apo-Lf but not holo-Lf chelated cellular iron, there was no difference between the two types of Lf in the neuroprotection. Our data indicate that iron overload increases the activated microglia releasing Lf. Lf plays protective role on ventral mesencephalon neurons against MPP(+), which is iron-chelating independent.
Insights
Iron overload stimulates microglia to release lactoferrin (Lf), which protects neurons from toxins. This neuroprotection by lactoferrin is independent of its iron-binding ability.
Area of Science:
- Neuroscience
- Biochemistry
- Cell Biology
Background:
- Lactoferrin (Lf) facilitates iron transport and possesses antioxidant/anti-inflammatory properties.
- In the brain, Lf is produced by activated microglia, and its receptor (LfR) is found on blood vessels and dopaminergic neurons.
- Microglia activation and nigral iron accumulation are implicated in Parkinson's disease (PD), with elevated Lf and LfR observed in PD cases.
Purpose of the Study:
- To investigate the relationship between iron, microglia activation, and lactoferrin (Lf) synthesis.
- To determine the role of Lf in protecting dopaminergic neurons against neurotoxins, particularly concerning its iron-binding capacity.
Main Methods:
- Assessed Lf synthesis in activated microglia under iron influence.
- Evaluated the neuroprotective effects of iron-free Lf (apo-Lf) and iron-saturated Lf (holo-Lf) against MPP+ in ventral mesencephalon neurons.
- Measured mitochondrial transmembrane potential, Cu/Zn-superoxide dismutase activity, and Bcl-2 expression.
Main Results:
- Iron significantly increased Lf synthesis in activated microglia.
- Both apo-Lf and holo-Lf demonstrated neuroprotective effects against MPP+.
- Neuroprotection mechanisms involved enhanced mitochondrial function, improved antioxidant activity, and increased Bcl-2 expression.
- While apo-Lf chelated cellular iron, both Lf forms provided similar neuroprotection, indicating an iron-chelating independent effect.
Conclusions:
- Iron overload prompts activated microglia to release Lf.
- Lf confers a protective role on ventral mesencephalon neurons against MPP+ toxicity.
- The neuroprotective function of Lf is independent of its iron-chelating properties.
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