Neuron-glia communication: metallothionein expression is specifically up-regulated by astrocytes in response to neuronal injury.
Recent data suggests that metallothioneins (MTs) are major neuroprotective proteins within the CNS. In this regard, we have recently demonstrated that MT-IIA (the major human MT-I/-II isoform) promotes neural recovery following focal cortical brain injury. To further investigate the role of MTs in cortical brain injury, MT-I/-II expression was examined in several different experimental models of cortical neuron injury. While MT-I/-II immunoreactivity was not detectable in the uninjured rat neocortex, by 4 days, following a focal cortical brain injury, MT-I/-II was found in astrocytes aligned along the injury site. At latter time points, astrocytes, at a distance up to several hundred microns from the original injury tract, were MT-I/-II immunoreactive. Induced MT-I/-II was found both within the cell body and processes. Using a cortical neuron/astrocyte co-culture model, we observed a similar MT-I/-II response following in vitro injury. Intriguingly, scratch wound injury in pure astrocyte cultures resulted in no change in MT-I/-II expression. This suggests that MT induction was specifically elicited by neuronal injury. Based upon recent reports indicating that MT-I/-II are major neuroprotective proteins within the brain, our results provide further evidence that MT-I/-II plays an important role in the cellular response to neuronal injury.
Chung
Roger S
RS
NeuroRepair Group, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia. rschung@utas.edu.au
Adlard
Paul A
PA
Dittmann
Justin
J
Vickers
James C
JC
Chuah
Meng Inn
MI
West
Adrian K
AK
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis* / Q000235:genetics; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D015854:Up-Regulation / Q000502:physiology*
D008668:Metallothionein