Extracellular signal-regulated kinase involvement in human astrocyte migration.
Glial scar formation occurs after virtually any injury to the brain. The migration of astrocytes into regions of brain injury underlies the formation of the glial scar. The exact role of the glial scar has yet to be elucidated, although it is likely to impair brain recovery. Understanding astrocyte migration is fundamental to understanding the formation of the glial scar. We have used human astrocytes (NT2A cells), derived from human NT2/D1 precursor cells to study astrocyte migration using an in vitro scratch wound model. Time-lapse microscopy and bromodeoxyuridine labeling revealed that the astrocytes migrated rather than proliferated across the scratch. Time course immunocytochemical studies showed that scratching human astrocytes induced the activation (phosphorylation) of ERK 1/2 at 10 min after scratch. The MEK 1/2 inhibitor U0126 inhibited both the ERK 1/2 phosphorylation and the migration of the astrocytes across the wound after scratch. Thus, the migration of human astrocytes after injury is partly initiated by activation of the MEK-ERK signalling pathway.
Lim
Joanne H
JH
Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
Gibbons
Hannah M
HM
O'Carroll
Simon J
SJ
Narayan
Pritika J
PJ
Faull
Richard L M
RL
Dragunow
Michael
M
D001253:Astrocytes / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism / Q000503:physiopathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002921:Cicatrix / Q000378:metabolism* / Q000503:physiopathology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005911:Gliosis / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects
D004791:Enzyme Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases