Journal
GLIA
Volume 62, Issue 5, Pages 751-762Publisher
WILEY
DOI: 10.1002/glia.22639
Keywords
amyotrophic lateral sclerosis; multiple sclerosis; neuroinflammation; oligodendroglial progenitors; protection; sigma receptors
Categories
Funding
- Investigator Initiated Award from Avanir Pharmeceuticals, Inc.
- Parker Webber Endowed Chair in Neurology (Detroit Medical Center/Wayne State University)
- National Multiple Sclerosis Society Collaborative Research Center Award
Ask authors/readers for more resources
Dextromethorphan (DM), a sigma receptor agonist and NMDA receptor antagonist, protects neurons from glutamate excitotoxicity, hypoxia and ischemia, and inhibits microglial activation, but its effects on differentiation and protection of cells in the oligodendroglial lineage are unknown. It is important to protect oligodendroglia (OL) to prevent demyelination and preserve axons, and to protect oligodendroglial progenitors (OPC) to optimize myelination during development and remyelination following damage. Enriched glial cultures from newborn rat brain were used 1-2 days or 6-8 days after shakeoff for OPC or mature OL. DM had large effects on glial proliferation in less mature cultures in contrast to small variable effects in mature cultures; 1 mu M DM stimulated proliferation of OPC by 4-fold, microglia (MG) by 2.5-fold and astroglia (AS) by 2-fold. In agreement with increased OPC proliferation, treatment of OPC with DM for 3 days increased the % of OPC relative to OL, with a smaller difference by 5 days, suggesting that maturation of OPC to OL was catching up by 5 days. DM at 2 and 20 mu M protected both OL and OPC from killing by glutamate as well as NMDA, AMPA, quinolinic acid, staurosporine, and reactive oxygen species (ROS). DM did not protect against kynurenic acid, and only modestly against NO. These agents and DM were not toxic to AS or MG at the concentrations used. Thus, DM stimulates proliferation of OPC, and protects both OL and OPC against excitotoxic and inflammatory insults.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available