Related Experiment Video
Updated: Jun 27, 2025
Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
M1 polarization induction by lead and amyloid peptides in microglial cells: Implications for neurodegeneration
Murumulla Lokesh1, Lakshmi Jaya Madhuri Bandaru1, Ajumeera Rajanna1
1Cell Biology Division, National Institute of Nutrition, Hyderabad, India.
Abstract:
Neurodegeneration in conditions like Alzheimer's and Parkinson's disease is influenced by genetic and environmental factors. This study explores the potential neurodegenerative effects of lead (Pb) toxicity and amyloid beta peptides (Aβp 1-40 and Aβp 25-35) by promoting M1 polarization in microglial cells. To this end, we investigated and observed that IC50 concentrations of Pb (22.8 μM) and Aβp 25-35(29.6 μM). Our results demonstrated significant Pb uptake (31.13% at 25 μM Pb) and increased intracellular ROS levels (77.1%) upon treatment with Pb in combination of both Aβp 1-40 and Aβp 25-35. Protein carbonylation significantly increased (73.12 nmol/mL) upon treatment with Pb in combination of both Aβp 1-40 and Aβp 25-35, indicating oxidative damage and compromised cellular defenses against oxidative stress along with elevated DNA oxidative damage (164.9 pg/mL of 8-OH-dG) upon treatment with Pb in combination with both Aβp 1-40 and Aβp 25-35. Microglial polarization showed elevated M1 markers (inducible nitric oxide synthase and cyclooxygenase 2) and reduced M2 markers (arginase-1 and cluster of differentiation 206), suggesting Pb's role in inducing neurodegenerative microglial polarization. These findings provide insights into the complex molecular events contributing to Pb-induced neurotoxicity and neurodegenerative diseases.
Insights
Lead (Pb) and amyloid beta peptides promote M1 microglial polarization, contributing to neurodegeneration. This study reveals Pb
Area of Science:
- Neuroscience
- Toxicology
- Cell Biology
Background:
- Neurodegenerative diseases like Alzheimer's and Parkinson's are linked to genetic and environmental factors.
- Microglial cells play a crucial role in neuroinflammation and disease progression.
- Lead (Pb) toxicity and amyloid beta peptides (Aβp) are implicated in neuronal damage.
Purpose of the Study:
- To investigate the neurotoxic effects of lead (Pb) and amyloid beta peptides (Aβp 1-40 and Aβp 25-35).
- To determine if Pb and Aβp promote M1 polarization in microglial cells, a key indicator of neuroinflammation.
- To elucidate the molecular mechanisms underlying Pb-induced neurotoxicity.
Main Methods:
- Determined IC50 concentrations for Pb and Aβp 25-35.
- Quantified Pb uptake and intracellular reactive oxygen species (ROS) levels.
- Assessed protein carbonylation and DNA oxidative damage (8-OH-dG).
- Analyzed microglial polarization by measuring M1 and M2 marker expression.
Main Results:
- Significant Pb uptake and increased ROS levels were observed upon treatment with Pb and Aβp.
- Elevated protein carbonylation and DNA oxidative damage indicated significant oxidative stress.
- Microglial cells showed increased M1 markers (iNOS, COX-2) and decreased M2 markers (Arg-1, CD206), confirming M1 polarization.
- IC50 concentrations were determined as 22.8 μM for Pb and 29.6 μM for Aβp 25-35.
Conclusions:
- Lead (Pb) exposure, in combination with amyloid beta peptides, induces oxidative stress and DNA damage in microglial cells.
- Pb promotes M1 polarization of microglial cells, suggesting a role in neuroinflammation and neurodegeneration.
- These findings offer insights into the molecular mechanisms of Pb-induced neurotoxicity and its contribution to neurodegenerative diseases.
More Related Videos
09:12Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
10:40Immunofluorescence Staining Using IBA1 and TMEM119 for Microglial Density, Morphology and Peripheral Myeloid Cell Infiltration Analysis in Mouse Brain
Published on: October 27, 2019
