Excitotoxic brain damage in the rat induces interleukin-1beta protein in microglia and astrocytes: correlation with the progression of cell death.
Interleukin-1 beta (IL-1beta) has been proposed as a mediator of several forms of brain damage, including that induced by excitotoxins. In vitro studies suggest that glial cells are the effector cells of IL-1beta-mediated neurodegeneration. We have investigated the expression of IL-1beta protein by glial cells in vivo in response to NMDA receptor-mediated excitotoxicity in the rat parietal cortex and striatum. Expression of IL-1beta by glial cells was investigated using immunocytochemistry 30 min to 7 days after infusion of the NMDA agonist cis-2,4-methanoglutamate (MGlu; 10 nmol) into the cortex. Early expression (1-4 h) of IL-1beta by microglia was directly related to lesion development. Later expression by microglia (up to 24 h), and by astrocytes (2-7 days), was widespread compared to the area involved in excitotoxic cell death and co-localised with areas of reactive gliosis. Infusion of MGlu into the striatum induced a similar temporal pattern of IL-1beta expression by microglia and astrocytes. However, IL-1beta-expressing glial cells were localised strictly to the area of striatal cell death. Infusion of PBS or a subtoxic dose of MGlu into the cortex or striatum induced only limited neuronal death and negligible glial IL-1beta expression. These studies reveal that IL-1beta is expressed specifically by microglia during the early response to excitotoxicity in the adult rat cortex and striatum. However, the widespread and delayed IL-1beta expression by astrocytes suggests diverse roles for IL-1beta in response to excitotoxicity.
School of Biological Sciences, University of Manchester, United Kingdom.
V L
VL
Pearson
N J
NJ
Rothwell
S
S
Toulmond
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis*; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology
D005971:Glutamates; D007375:Interleukin-1; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; C066302:2,4-methanoglutamate