Allan SM; Lawrence CB; Rothwell NJ.
Interleukin-1 beta and interleukin-1 receptor antagonist do not affect glutamate release or calcium entry in rat striatal synaptosomes, Mol Psychiatry 3(2) :178-82, 1998.
Abstract
The cytokine interleukin-1 beta (IL-1 beta) has been implicated in various forms of neurodegeneration, and several lines of evidence indicate that it also modulates synaptic transmission in the central nervous system. Excessive release of the excitatory neurotransmitter L-glutamate results in cell death and probably mediates many neurodegenerative conditions. We set out to test the hypothesis that involvement of IL-1 beta in neurodegeneration results in some interaction with excitatory amino acid-mediated synaptic transmission in the rat striatum, either by modifying glutamate release or actions. Presynaptic effects of IL-1 beta and the IL-1 receptor antagonist (IL-1ra) on glutamate release and calcium entry were investigated in isolated nerve terminals (synaptosomes) prepared from the striatum. In order to evaluate the involvement of IL-1 in neuronal damage caused by glutamate receptor over-activation, the effect of IL-1ra was studied on N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor-mediated brain damage in the rat striatum and cortex in vivo. Neither rat recombinant IL-1 beta (rrIL-1 beta: 0.01-2 nM) or human recombinant IL-1ra (hrIL-1ra: 0.2 microM) had any significant effect on the KCl-evoked glutamate efflux or calcium entry in striatal synaptosomes, indicating that their actions are unlikely to be presynaptic. In contrast, intrastriatal infusion of hrIL-1ra markedly inhibited (by 43-46%, P < 0.05) neuronal damage caused by striatal NMDA or AMPA receptor activation in the rat in vivo, whereas no effect was seen on damage induced in the cortex. Thus, our data suggest that IL-1 beta and IL-1ra influence neuronal damage in the striatum by acting to modify events that occur after excitatory amino acid receptor activation
Return to Neurotoxicity of Cytokines References