The cytokine interleukin-1 (IL-1) 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. 1 Excessive release of the excitatory neurotransmitter L-glutamate results in cell death and probably mediates many neurodegenerative conditions. 2 We set out to test the hypothesis that involvement of IL-1 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 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 ␣-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 (rrIL-1: 0.01-2 nM) or human recombinant IL-1ra (hrIL-1ra: 0.2 M) 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 Ͻ Ͻ Ͻ 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 and IL-1ra influence neuronal damage in the striatum by acting to modify events that occur after excitatory amino acid receptor activation.In the presence of calcium (Ca 2+ ) a progressive increase in glutamate efflux from striatal synaptosomes (4.30 ± 0.35 nmol mg −1 protein per 5 min; n = 6; Figure 1a) was observed following addition of vehicle. Depolarisation by exposure to 30 mM KCl resulted in a significant increase in the release of glutamate above the vehicle level (6.12 ± 0.49 nmol glutamate mg −1 protein per 5 min; P Ͻ 0.05; n = 6; Figure 1a). The release
Galanin‐like peptide (GALP) is thought to play a role in energy balance within the central nervous system. Experimental evidence shows that GALP has dichotomous actions on energy homeostasis; producing orexigenic effects in the short‐term, but anorexigenic effects over the longer‐term. These anorexic actions of GALP are very similar to that seen after peripheral or central injection of the cytokine interleukin‐1 (IL‐1). Thus the aim of this study was to test the hypothesis that IL‐1 mediates the effects of GALP on energy balance. Intracerebroventricular (icv) injection of GALP (1.6 nmol) in male Sprague‐Dawley rats stimulated food intake over 1 h, but decreased feeding, body weight at 24 h and cause a rise in core body temperature over 8 h (indirect evidence of an increase in energy expenditure). These longer‐term actions were inhibited by co‐infusion of the IL‐1 receptor antagonist, IL‐1ra. However, IL‐1ra had no effect on GALP‐induced acute stimulation of feeding. GALP injection (icv) also stimulated production of IL‐1 protein in selected brain areas, such as the periventricular brain region and these IL‐1 expressing cells were microglia. These data suggest GALP induces expression of IL‐1 in the brain and the anorexic and febrile actions of GALP are mediated by this cytokine.
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