Dopamine D2 and D3 receptor agonists limit oligodendrocyte injury caused by glutamate oxidative stress and oxygen/glucose deprivation.
Dopamine receptor activation is thought to contribute adversely to several neuropathological disorders, including Parkinson's disease and schizophrenia. In addition, dopamine may have a neuroprotective role: dopamine receptor agonists are reported to protect nerve cells by virtue of their antioxidant properties as well as by receptor-mediated mechanisms. White matter injury can also be a significant factor in neurological disorders. Using real-time RT-PCR, we show that differentiated rat cortical oligodendrocytes express dopamine D2 receptor and D3 receptor mRNA. Oligodendrocytes were vulnerable to oxidative glutamate toxicity and to oxygen/glucose deprivation injury. Agonists for dopamine D2 and D3 receptors provided significant protection of oligodendrocytes against these two forms of injury, and the protective effect was diminished by D2 and D3 antagonists. Levels of oligodendrocyte D2 receptor and D3 receptor protein, as measured by Western blotting, appeared to increase following combined oxygen and glucose deprivation. Our results suggest that dopamine D2 and D3 receptor activation may play an important role in oligodendrocyte protection against oxidative glutamate toxicity and oxygen-glucose deprivation injury.
Rosin
Claudia
C
Neurology and GI Centre of Excellence for Drug Discovery, GlaxoSmithKline Research and Development Limited, Harlow, United Kingdom.
Colombo
Sergio
S
Calver
Andrew A
AA
Bates
Timothy E
TE
Skaper
Stephen D
SD
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000235:genetics* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000235:genetics / Q000378:metabolism
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D018698:Glutamic Acid; D005947:Glucose; D010100:Oxygen