Role of the IL-1 Pathway in Dopaminergic Neurodegeneration and Decreased Voluntary Movement

Interleukin-1 (IL-1), a proinflammatory cytokine synthesized and released by activated microglia, can cause dopaminergic neurodegeneration leading to Parkinsons disease (PD). However, it is uncertain whether IL-1 can act directly, or by exacerbating the harmful actions of other brain insults. To ascertain the role of the IL-1 pathway on dopaminergic neurodegeneration and motor skills during aging, we compared mice with impaired [caspase-1 knockout (casp1(-/-))] or overactivated IL-1 activity [IL-1 receptor antagonist knockout (IL-1ra(-/-))] to wild-type (wt) mice at young and middle age. Their motor skills were evaluated by the open-field and rotarod tests, and quantification of their dopamine neurons and activated microglia within the substantia nigra were performed by immunohistochemistry. IL-1ra(-/-) mice showed an age-related decline in motor skills, a reduced number of dopamine neurons, and an increase in activated microglia when compared to wt or casp1(-/-) mice. Casp1(-/-) mice had similar changes in motor skills and dopamine neurons, but fewer activated microglia cells than wt mice. Our results suggest that the overactivated IL-1 pathway occurring in IL-1ra(-/-) mice in the absence of inflammatory interventions (e.g., intracerebral injections performed in animal models of PD) increased activated microglia, decreased the number of dopaminergic neurons, and reduced their motor skills. Decreased IL-1 activity in casp1(-/-) mice did not yield clear protective effects when compared with wt mice. In summary, in the absence of overt brain insults, chronic activation of the IL-1 pathway may promote pathological aspects of PD per se, but its impairment does not appear to yield advantages over wt mice.Funding Agencies|John Curtin School of Medical Research, The Australian National University</p

Age-Related Comparisons of Evolution of the Inflammatory Response After Intracerebral Hemorrhage in Rats

In the hours to days after intracerebral hemorrhage (ICH), there is an inflammatory response within the brain characterized by the infiltration of peripheral neutrophils and macrophages and the activation of brain-resident microglia and astrocytes. Despite the strong correlation of aging and ICH incidence, and increasing information about cellular responses, little is known about the temporal- and age-related molecular responses of the brain after ICH. Here, we monitored a panel of 27 genes at 6 h and 1, 3, and 7 days after ICH was induced by injecting collagenase into the striatum of young adult and aged rats. Several molecules (CR3, TLR2, TLR4, IL-1β, TNFα, iNOS, IL-6) were selected to reflect the classical activation of innate immune cells (macrophages, microglia) and the potential to exacerbate inflammation and damage brain cells. Most of the others are associated with the resolution of innate inflammation, alternative pathways of macrophage/microglial activation, and the repair phase after acute injury (TGFβ, IL-1ra, IL-1r2, IL-4, IL-13, IL-4Rα, IL-13Rα1, IL-13Rα2, MRC1, ARG1, CD163, CCL22). In young animals, the up-regulation of 26 in 27 genes (not IL-4) was detected within the first week. Differences in timing or levels between young and aged animals were detected for 18 of 27 genes examined (TLR2, GFAP, IL-1β, IL-1ra, IL-1r2, iNOS, IL-6, TGFβ, MMP9, MMP12, IL-13, IL-4Rα, IL-13Rα1, IL-13Rα2, MRC1, ARG1, CD163, CCL22), with a generally less pronounced or delayed inflammatory response in the aged animals. Importantly, within this complex response to experimental ICH, the induction of pro-inflammatory, potentially harmful mediators often coincided with resolving and beneficial molecules

Verbesserungs-Vorschläge für das Volks-Schulwesen Deutschlands, oder Darstellungen, wie das Volks-Schulwesen, den Anforderung der Zeit gemäß, werden muß : den Volksvertretern Deutschlands und den Unterrichts-Ministerien zur geneigten Berücksichtigung vertrauungsvoll gewidmet

Boberach: Die Volksschulen sollen verstaatlicht, ihre Lehrer besser besoldet werdenvon Werner HerxIn Fraktu

Expression and roles of interleukin-1B in central nervous system trauma: regulation of astrogliosis and ciliary neurotrophic factor production

Bibliography: p. 115-18

Berichte - Dokumentation - Chronik

BerichteRolf PitschChancen des religiösen Buches. Eine Untersuchung der Situation des katholischen BuchmarktesChristoph AremVon Lese-Müdigkeit keine Spur. 150 Jahre BorromäusvereinZwei private katholische Rundfunkinitiativen. Radio Campanile erhielt Sendelizenz Glemp wünscht Katholisches Fernsehen in Polen DokumentationMedien, Gewalt und Frieden. Ansprache von Kardinal Carlo Maria Martini, Erzbischof von Mailand, beim 17. UCIP-Weltkongreß in Graz am 13. September 1995 Henry HerxImages of violence in a world of conflict. Statement at the 17. UCIP-Worldcongress 1995 in GrazP. Laslo LukacsDas Europäische Katholische NachrichtenforumChronik

Development of immortalized human cerebromicrovascular endothelial cell line as an in vitro model of the human blood-brain barrier

NRC publication: Ye