Related Experiment Video

Updated: Jun 23, 2026

Correlative Light and Electron Microscopy to Study Microglial Interactions with β-Amyloid Plaques
10:52

Correlative Light and Electron Microscopy to Study Microglial Interactions with β-Amyloid Plaques

Published on: June 1, 2016

11.5K

Ferroptosis of Microglia in Aging Human White Matter Injury

Philip A Adeniyi1, Xi Gong1, Ellie MacGregor1

  • 1Departments of Pediatrics, Oregon Health & Science University, Portland, OR.

Annals of Neurology
|August 22, 2023
PubMed
Abstract

Insights

Degenerating microglia (DM) in aging white matter (WM) lesions accumulate iron and show signs of oxidative stress and DNA damage, suggesting ferroptosis contributes to WM injury.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Pathology

Background:

  • Microglia play crucial roles in brain health and disease.
  • Aging is associated with altered microglial function and increased susceptibility to neurodegenerative diseases.
  • White matter (WM) integrity is vital for cognitive function, and its degeneration contributes to cognitive decline.

Purpose of the Study:

  • To define the core features of degenerating microglia (DM) in aging human WM lesions.
  • To investigate the molecular mechanisms underlying DM degeneration.
  • To explore the role of DM in remyelination failure and WM injury.

Main Methods:

  • Analysis of postmortem human brain tissue from aging WM lesions.
  • Immunofluorescence staining to identify cellular markers.
  • Gene expression analysis to investigate molecular pathways.

Main Results:

  • DM accumulate myelin debris, ferritin, and lipid droplets (PLIN2).
  • DM exhibit lipid peroxidation, increased TOM20 expression (oxidative stress), and DNA fragmentation (phospho-histone H2A.X).
  • A unique set of ferroptosis-related genes, involving iron and oxidative stress, are preferentially expressed in WM injury.

Conclusions:

  • Ferroptosis is a key mechanism of WM injury in neurodegenerative conditions like Alzheimer's disease and vascular dementia.
  • WM DM represent a novel therapeutic target to mitigate WM injury and cognitive impairment progression.

More Related Videos

Immunofluorescence Staining Using IBA1 and TMEM119 for Microglial Density, Morphology and Peripheral Myeloid Cell Infiltration Analysis in Mouse Brain10:40

Immunofluorescence Staining Using IBA1 and TMEM119 for Microglial Density, Morphology and Peripheral Myeloid Cell Infiltration Analysis in Mouse Brain

Published on: October 27, 2019

32.3K
Assessing Iron Deposition in the Brains of 5xFAD Mice by Perls'/DAB Staining07:32

Assessing Iron Deposition in the Brains of 5xFAD Mice by Perls'/DAB Staining

Published on: May 23, 2025

331

Related Concept Videos

Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
The Effect of Aging on Tissues01:19

The Effect of Aging on Tissues

Several body functions deteriorate with age. The external signs of aging are easily identifiable. For example, the skin becomes dry, less elastic, and thins out, forming wrinkles. The skin of the face begins to appear looser due to a decrease in the levels of elastic and collagen fibers in the connective tissue. Additionally, melanin production in the hair follicle decreases with age, resulting in gray hair. Moreover, the senses of sight and hearing decline, so glasses and hearing aids may...
Bone Disorders01:29

Bone Disorders

Aging and its effect on bone remodeling is the most common cause of bone disorders. In young and healthy people, bone deposition and resorption happen at an equal rate to maintain optimal bone health.
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
Lifecycle of Erythrocytes01:22

Lifecycle of Erythrocytes

Erythrocytes, also known as red blood cells, constantly move through blood capillaries. As a result, they damage their plasma membrane due to the continuous friction. Typically, after 100 to 120 days, erythrocytes become rigid and fragile as they wear out. As they pass through small vessels in the spleen and liver, they can get trapped and break apart into fragments.
The resident phagocytic macrophages deal with these damaged cells by engulfing them and separating their globin and heme groups.
Aging01:26

Aging

Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in aging.
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
Development of Human Microbiota01:30

Development of Human Microbiota

The human microbiota begins developing at birth and undergoes continual change as we age. Infancy marks a critical period of microbial sensitivity, offering a “window of opportunity” during which beneficial microbes help mature the immune system. By age three, children typically develop a more stable and diverse microbial community. Newborns acquire microbes from their immediate environment; vaginal delivery favors maternal vaginal microbes, while cesarean births favor microbes from the skin...