Lesion-associated microglia and macrophages mediate corralling and react with massive phagocytosis for debris clearance and wound healing after LPS-induced dopaminergic depletion

Altres ajuts: Acord transformatiu CRUE-CSICNeuroinflammation contributes to neuronal degeneration in Parkinson's disease (PD). However, how brain inflammatory factors mediate the progression of neurodegeneration is still poorly understood. Experimental models of PD have shed light on the understanding of this phenomenon, but the exploration of inflammation-driven models is necessary to better characterize this aspect of the disorder. The use of lipopolysaccharide (LPS) to induce a neuroinflammation-mediated neuronal loss is useful to induce reliable elimination of dopaminergic neurons. Nevertheless, how this model parallels the PD-like neuroinflammation is uncertain. In the present work, we used the direct LPS injection as a model inductor to eliminate dopaminergic neurons of the substantia nigra pars compacta (SNpc) in rats and reevaluated the inflammatory reaction. High-resolution 3D histological examination revealed that, although LPS induced a reliable elimination of SNpc dopaminergic neurons, it also generated a massive inflammatory response. This inflammation-mediated injury was characterized by corralling, a damaged parenchyma occupied by a vast population of lesion-associated microglia and macrophages (LAMMs) undertaking wound compaction and scar formation, surrounded by highly reactive astrocytes. LAMMs tiled the entire lesion and engaged in long-standing phagocytic activity to resolve the injury. Additionally, modeling LPS inflammation in a cell culture system helped to understand the role of phagocytosis and cytotoxicity in the initial phases of dopaminergic degeneration and indicated that LAMM-mediated toxicity and phagocytosis coexist during LPS-mediated dopaminergic elimination. However, this type of severe inflammatory-mediated injury, and subsequent resolution appear to be different from the ageing-related PD scenario where the architectural structure of the parenchyma is mostly preserved. Thus, the necessity to explore new experimental models to properly mimic the inflammatory compound observed in PD degeneration

Ecological determinants of pathogen infection in howler monkeys

Infectious diseases caused by pathogens are now recognized as one of the most important threats to primate conservation. The fact that howler monkeys (Alouatta spp.) are widely distributed from Southern Mexico to Northern Argentina, inhabit a diverse array of habitats, and are considered pioneers, particularly adapted to exploit marginal habitats, provides an opportunity to explore general trends of parasitism and evaluate the dynamics of infectious diseases in this genus. We take a meta-analysis approach to examine the effect of ecological and environmental variables on parasitic infection using data from 7 howler monkey species at more than 35 sites throughout their distribution. We found that different factors including precipitation, latitude, altitude, and human proximity may infl uence parasite infection depending on the parasite type. We also found that parasites infecting howler monkeys followed a right-skewed distribution, suggesting that only a few individuals harbor infections. This result highlights the importance of collecting large sample sizes when developing these kinds of studies. We suggest that future studies should focus on obtaining fi ne-grained measurements of ecological and microclimate changes to provide better insights into the proximate factors that promote parasitism.Fil: Martinez Mota, Rodolfo. University of Illinois at Urbana-Champaign; Estados UnidosFil: Kowalewski, Miguel Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia". Estación Biológica de Usos Múltiples (Sede Corrientes); ArgentinaFil: Gillespie, Thomas R.. Emory University; Estados Unido