Related Experiment Video
Updated: Mar 6, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Microglia-derived IL-1β contributes to axon development disorders and synaptic deficit through p38-MAPK signal
Qianpeng Han1,2,3, Qiongyu Lin1,2, Peixian Huang2,4
1Southern Medical University, Guangzhou, 510515, People's Republic of China.
Background:
Axon development plays a pivotal role in the formation of synapse, nodes of Ranvier, and myelin sheath. Interleukin-1β (IL-1β) produced by microglia may cause myelination disturbances through suppression of oligodendrocyte progenitor cell maturation in the septic neonatal rats. Here, we explored if a microglia-derived IL-1β would disturb axon development in the corpus callosum (CC) following lipopolysaccharide (LPS) administration, and if so, whether it is associated with disorder of synapse formation in the cerebral cortex and node of Ranvier.
Methods:
Sprague-Dawley rats (1-day old) in the septic model group were intraperitoneally administrated with lipopolysaccharide (1 mg/kg) and then sacrificed for detection of IL-1β, interleukin-1 receptor (IL-1R1), neurofilament-68, neurofilament-160, and neurofilament-200, proteolipid, synaptophysin, and postsynaptic density 95 (PSD95) expression by western blotting and immunofluorescence. Electron microscopy was conducted to observe alterations of axonal myelin sheath and synapses in the cortex, and proteolipid expression was assessed using in situ hybridization. The effect of IL-1β on neurofilament and synaptophysin expression in primary neuron cultures was determined by western blotting and immunofluorescence. P38-MAPK signaling pathway was investigated to determine whether it was involved in the inhibition of IL-1β on neurofilament and synaptophysin expression.
Results:
In 1-day old septic rats, IL-1β expression was increased in microglia coupled with upregulated expression of IL-1R1 on the axons. The expression of neurofilament-68, neurofilament-160, and neurofilament-200 (NFL, NFM, NFH) and proteolipid (PLP) was markedly reduced in the CC at 7, 14, and 28 days after LPS administration. Simultaneously, cortical synapses and mature oligodendrocytes were significantly reduced. By electron microscopy, some axons showed smaller diameter and thinner myelin sheath with damaged ultrastructure of node of Ranvier compared with the control rats. In the cerebral cortex of LPS-injected rats, some axo-dendritic synapses appeared abnormal looking as manifested by the presence of swollen and clumping of synaptic vesicles near the presynaptic membrane. In primary cultured neurons incubated with IL-1β, expression of NFL, NFM, and synaptophysin was significantly downregulated. Furthermore, p38-MAPK signaling pathway was implicated in disorder of axon development and synaptic deficit caused by IL-1β treatment.
Conclusions:
The present results suggest that microglia-derived IL-1β might suppress axon development through activation of p38-MAPK signaling pathway that would contribute to formation disorder of cortical synapses and node of Ranvier following LPS exposure.
Insights
Interleukin-1β (IL-1β) from microglia disrupts axon development and synapse formation in neonatal rats following lipopolysaccharide (LPS) exposure, mediated by the p38-MAPK pathway. This leads to impaired myelination and synaptic deficits.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Axon development is crucial for neural circuit formation, including synapses and myelin.
- Microglia-derived Interleukin-1β (IL-1β) is implicated in myelination disturbances in neonatal sepsis models.
- Lipopolysaccharide (LPS) administration in neonatal rats can induce inflammatory responses affecting brain development.
Purpose of the Study:
- To investigate if microglia-derived IL-1β disrupts axon development in the corpus callosum (CC) after LPS administration.
- To determine if IL-1β-induced axon disturbances are associated with impaired synapse formation in the cerebral cortex.
- To explore the role of the p38-MAPK signaling pathway in IL-1β-mediated effects on axon and synapse development.
Main Methods:
- Established a septic neonatal rat model using LPS administration.
- Quantified expression of IL-1β, IL-1R1, neurofilaments (NFL, NFM, NFH), and proteolipid (PLP) via Western blotting and immunofluorescence.
- Utilized electron microscopy to assess axonal myelin sheath and synaptic ultrastructure.
- Investigated the effect of IL-1β on primary neuron cultures and the involvement of the p38-MAPK pathway.
Main Results:
- LPS administration increased IL-1β in microglia and IL-1R1 on axons, with reduced NFL, NFM, NFH, and PLP expression in the CC.
- Observed significant reductions in cortical synapses and mature oligodendrocytes, along with thinner myelin sheaths and abnormal nodes of Ranvier.
- IL-1β treatment in primary neurons downregulated NFL, NFM, and synaptophysin expression, implicating the p38-MAPK pathway.
Conclusions:
- Microglia-derived IL-1β suppresses axon development via p38-MAPK activation following LPS exposure.
- This suppression contributes to the disordered formation of cortical synapses and nodes of Ranvier.
- The findings highlight a critical inflammatory mechanism impacting early brain development and synaptic integrity.
