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Ferulic Acid Rescues LPS-Induced Neurotoxicity via Modulation of the TLR4 Receptor in the Mouse Hippocampus
- Source :
- Molecular Neurobiology, 56(4), 2774-2790. Springer, Cham
- Publication Year :
- 2019
- Publisher :
- Springer, Cham, 2019.
-
Abstract
- Microglia play a crucial role in the inflammatory brain response to infection. However, overactivation of microglia is neurotoxic. Toll-like receptor 4 (TLR4) is involved in microglial activation via lipopolysaccharide (LPS), which triggers a variety of cytotoxic pro-inflammatory markers that produce deleterious effects on neuronal cells. Ferulic acid (FA) is a phenolic compound that exerts antioxidant and anti-inflammatory effects in neurodegenerative disease. However, the manner in which FA inhibits neuroinflammation-induced neurodegeneration is poorly understood. Therefore, we investigated the anti-inflammatory effects of FA against LPS-induced neuroinflammation in the mouse brain. First, we provide evidence that FA interferes with TLR4 interaction sites, which are required for the activation of microglia-induced neuroinflammation, and further examined the potential mechanism of its neuroprotective effects in the mouse hippocampus using molecular docking simulation and immunoblot analysis. Our results indicated that FA treatment inhibited glial cell activation, p-JNK, p-NFKB, and downstream signaling molecules, such as iNOS, COX-2, TNF-, and IL-1, in the mouse hippocampus and BV2 microglial cells. FA treatment strongly inhibited mitochondrial apoptotic signaling molecules, such as Bax, cytochrome C, caspase-3, and PARP-1, and reversed deregulated synaptic proteins, including PSD-95, synaptophysin, SNAP-25, and SNAP-23, and synaptic dysfunction in LPS-treated mice. These findings demonstrated that FA treatment interfered with the TLR4/MD2 complex binding site, which is crucial for evoking neuroinflammation via microglia activation and inhibited NFKB likely via a JNK-dependent mechanism, which suggests a therapeutic implication for neuroinflammation-induced neurodegeneration.
- Subjects :
- Lipopolysaccharides
Male
0301 basic medicine
NF-KAPPA-B
Apoptosis
Hippocampus
Cognition
0302 clinical medicine
Neuroinflammation
TLR4
IN-VIVO
Microglia
Chemistry
Neurodegeneration
NF-kappa B
ROS
Mitochondria
Up-Regulation
Cell biology
medicine.anatomical_structure
Neurology
Neurotoxicity Syndromes
Inflammation Mediators
Signal transduction
Cell activation
Signal Transduction
EXPRESSION
Synaptic dysfunction
LIPOPOLYSACCHARIDE-INDUCED NEUROINFLAMMATION
LPS
Coumaric Acids
INDUCED OXIDATIVE STRESS
Neuroscience (miscellaneous)
INHIBITION
Neuroprotection
Cell Line
SIGNALING PATHWAYS
03 medical and health sciences
Cellular and Molecular Neuroscience
medicine
Animals
Inflammation
TOLL-LIKE RECEPTORS
JNK Mitogen-Activated Protein Kinases
Neurotoxicity
medicine.disease
MICROGLIAL ACTIVATION
Mice, Inbred C57BL
Toll-Like Receptor 4
Oxidative Stress
030104 developmental biology
nervous system
CELL-DEATH
Astrocytes
Nerve Degeneration
Synapses
Biomarkers
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 15591182 and 08937648
- Volume :
- 56
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Molecular Neurobiology
- Accession number :
- edsair.doi.dedup.....831e1c2c26d0293697cd9f170b47b653