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Updated: Sep 27, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Triggering microglia through toll-like receptor 2 pathway induced interferon β expression in cell and animal model of
Nooshin Heshmati-Fakhr1,2, Fattah Sotoodehnejadnematalahi2, Niloufar Yousefi1,2
1Department of Physiology and Pharmacology, Pasteur Institute of Iran.
Abstract:
Synaptic function and memory performance are disrupted by soluble form of β-amyloid (Aβ). In the previous study, we found that early activation of microglia by toll-like receptor 2 (TLR2) attenuated Alzheimer's disease-associated cognitive deficit. This study was designed to investigate whether pretreatment with the TLR2 receptor ligand can regulate microglia to produce interferon β (INFβ) in a rat model of Alzheimer's disease. For this purpose, the BV-2 cell line was cultured in a 24-well plate, treated with Pam3Cys (1 μg/ml), and then incubated with oligomeric Aβ for 24 h. The expression of TRIF, IRF3, and INFβ was measured by western blot technique. For in-vivo study, bilateral guide cannulas were streotaxically implanted in the right and left lateral ventricles. Pam3Cys/vehicle was microinjected into the right ventricle every 3 days. Two weeks later, an osmotic pump was inserted into the left ventricle to microinfuse oligomeric Aβ/placebo over 14 days. In the meanwhile, treatment with Pam3Cys was continued every 3 days. Then, expression of TRIF, IRF3, and INFβ was measured in the hippocampus. The results showed that although oligomeric Aβ could not alter the expression of these proteins at the cell and tissue level, treatment with Pam3Cys resulted in enhanced expression of them at both cell culture and hippocampal tissue following treatment with oligomeric Aβ. It is concluded that stimulation of microglia through TLR2 pathway induces INFβ expression, which may in part mediate neuroprotection against oligomeric Aβ.
Insights
Toll-like receptor 2 (TLR2) activation in microglia induces interferon beta (INFβ) production. This neuroprotective mechanism may help combat cognitive deficits associated with Alzheimer's disease and amyloid beta (Aβ).
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Soluble beta-amyloid (Aβ) disrupts synaptic function and memory, contributing to Alzheimer's disease (AD).
- Previous research indicated that early microglial activation via toll-like receptor 2 (TLR2) can mitigate AD-related cognitive deficits.
Purpose of the Study:
- To investigate if TLR2 ligand pretreatment can modulate microglia to produce interferon beta (INFβ).
- To assess the effect of TLR2 activation on INFβ production in a rat model of Alzheimer's disease.
Main Methods:
- In vitro: BV-2 microglial cells were treated with Pam3Cys (TLR2 ligand) and then oligomeric Aβ. TRIF, IRF3, and INFβ expression were analyzed.
- In vivo: Rats received stereotaxic implantation of cannulas. Pam3Cys or vehicle was microinjected, followed by oligomeric Aβ or placebo infusion. Hippocampal TRIF, IRF3, and INFβ expression were measured.
Main Results:
- Oligomeric Aβ alone did not alter TRIF, IRF3, or INFβ expression in cell cultures or hippocampal tissue.
- Pam3Cys treatment significantly enhanced the expression of TRIF, IRF3, and INFβ in both cell cultures and hippocampal tissue after Aβ exposure.
Conclusions:
- Stimulation of microglia via the TLR2 pathway induces interferon beta (INFβ) expression.
- INFβ induction may play a partial role in neuroprotection against the detrimental effects of oligomeric Aβ in Alzheimer's disease models.
