Phosphatidylinositol 3-kinase/protein kinase Cδ activation induces close homolog of adhesion molecule L1 (CHL1) expression in cultured astrocytes

Glia, 2010 · DOI: 10.1002/glia.20925 · Published: February 1, 2010

Simple Explanation

The study investigates how astrocytes, a type of brain cell, increase production of a molecule called CHL1 after spinal cord injury. This increase can hinder nerve regeneration. The research found that a bacterial substance, LPS, causes astrocytes to produce more CHL1. This process involves specific molecular pathways inside the cells, including PI3K and PKCδ. Blocking these pathways reduces CHL1 production and promotes nerve growth in lab experiments, suggesting potential therapeutic targets for spinal cord injuries.

Study Duration

Not specified

Participants

Primary cultures of mouse cerebral astrocytes

Evidence Level

Not specified

Key Findings

1
LPS upregulates CHL1 expression in astrocytes via a PI3K/PKCδ-dependent pathway.
2
PKCδ activation and translocation are crucial for LPS-induced CHL1 upregulation.
3
Inhibition of PI3K and ERK1/2 pathways reduces LPS-induced CHL1 expression and NF-κB activation.

Research Summary

This study investigates the molecular mechanisms underlying the upregulation of CHL1 expression in reactive astrocytes following spinal cord injury (SCI). It demonstrates that bacterial lipopolysaccharide (LPS) stimulates astrogliosis, leading to increased CHL1 expression in primary cultures of mouse cerebral astrocytes. The findings reveal that LPS-induced CHL1 upregulation is mediated through a phosphatidylinositol 3-kinase (PI3K)/protein kinase Cδ (PKCδ)-dependent pathway, involving ERK1/2 phosphorylation and nuclear translocation of nuclear factor κB (NF-κB). Furthermore, the study shows that elevated CHL1 expression by reactive astrocytes inhibits hippocampal neurite outgrowth in cocultures, suggesting that reducing PI3K/PKCδ activity could benefit axonal regeneration after SCI.

Practical Implications

Therapeutic Target Identification

Reduction of PI3K/PKCδ activity represents a potential therapeutic target to downregulate CHL1 expression.

Axonal Regeneration Enhancement

Downregulating CHL1 expression may benefit axonal regeneration after SCI.

Glial Scar Modulation

Targeting PI3K/PKCδ/MAP kinase pathways may attenuate CHL1 expression by the glial scar.

Study Limitations

1
The study is conducted in vitro using primary cultures of mouse astrocytes, which may not fully replicate the in vivo environment of spinal cord injury.
2
The specific mechanisms of CHL1 regulation by MAP kinase pathway require further dissection.
3
The study does not fully elucidate the signal transduction pathways upstream and downstream of the MAP kinase pathway.

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