Glia
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Interleukins (IL)-1 alpha, beta and IL-6 may play essential roles in early inflammatory processes in response to degenerating cholinergic cells observed in the basal forebrain of Alzheimer patients. To address this question in vivo, two distinct lesion paradigms were used. A specific and selective basal forebrain cholinergic cell loss was achieved by a single intracerebroventricular application of the cholinergic immunotoxin, 192IgG-saporin. ⋯ In contrast, hippocampal administration of lipopolysaccharides/interferon-gamma resulted in expression of IL-1 alpha in microglial but not astroglial cells. These in vivo studies clearly demonstrate that the cellular expression of IL-1 alpha, IL-1 beta, and IL-6 in the brain is differentially regulated depending on the kind of injury producing the inflammatory response in the brain. The data suggest that each glial cell seems to be equally capable of expressing a number of various cytokines, but it depends on the kind of stimulus which temporal and cellular cascade of cytokine expression pattern is initiated under a particular pathological condition in the brain.
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An extracellular calcium (Ca2+o)-sensing receptor (CaR) plays crucial roles in maintaining systemic calcium homeostasis. The CaR is also expressed in other cells uninvolved in systemic mineral ion homeostasis, including keratinocytes, fibroblasts, and neurons. In brain the CaR is widely distributed, being particularly abundant in neurons in subfornical organ, cingulate cortex, hippocampus, and cerebellum. ⋯ Patch clamp analysis in the cell-attached mode revealed that raising Ca2+o from 0.75 to 1.75 or 2.75 mM produced approximately threefold increases in the open state probability (Po) of an outward K+ channel with a conductance of approximately 88 pS. A specific "calcimimetic" CaR activator, R-467 (0.5 microM), activated this K+ channel similarly, while its less active stereoisomer, S-467, did not. Thus U87 astrocytoma cells express both CaR mRNA and protein, and the receptor activates an outward K+ channel previously suggested to be involved in membrane polarization and cellular excitability.
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Three different cell markers were studied in rats to note changes in the immunoreactivity (IR) in the lumbar spinal cord 1 to 84 days following partial sciatic nerve ligation (PSNL). Alteration in average IR were studied for complement receptor C3bi (OX42; microglia), major histocompatibility complex II (OX6; microglia), and glia fibrillary acidic protein (GFAP; astroglia). Thirty-four female rats underwent ligation of approximately 1/2 of the sciatic nerve (PSNL). ⋯ Both GFAP IR and OX42 IR were found to linearly correlate with allodynic behavior with OX42 IR being more statistically significant. Correlation of OX42 IR in only the upper portion of the dorsal horn (not including the neck) resulted in an even a greater level of significance. These findings demonstrate that microglia and astroglia are activated following PSNL and that their increase in IR correlates with the development of allodynic behavior.
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In mixed glial cell cultures from cerebral cortices of newborn rats, endotoxin induces inducible nitric oxide (iNOS), nitric oxide (NO), and interleukin-1 beta (IL-1 beta) production in microglial cells. Earlier we demonstrated that endotoxin induced iNOS but not IL-1 beta expression in microglial cells is inhibited by the presence of astroglial cells. In the present paper we describe studies on the mechanism by which astroglial cells exert selective suppressive action on iNOS expression by microglial cells. ⋯ Incubation of the mixed glial cell culture with these TGF beta antibodies (3 micrograms/ml) markedly increased endotoxin-induced NO production and iNOS expression in microglial cells, whereas the production of IL-1 beta was not affected. The antibodies against TGF beta 1 and TGF beta 2 marginally increased NO production in pure microglial cell cultures, nonetheless in cultures of purified microglial cells recombinant TGF beta 1 and TGF beta 2 together with endotoxin inhibited NO production. We conclude that the presence of astroglial cells is essential for the inhibitory effect of TGF beta on NO production by microglial cells (possibly) by activation of TGF beta or by increasing the sensitivity of microglial cells for TGF beta.