Redescubriendo el espinal pampeano

Fil: Soibelzon, Esteban. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Paleontología Vertebrados; ArgentinaFil: Negrete, Javier. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo; ArgentinaFil: Ciai, Dante N.. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo; ArgentinaFil: Depino, Emiliano A.. Instituto de Bio y Geociencias del NOA; Argentin

Evolutionary history of the Galápagos Rail Revealed by ancient mitogenomes and modern samples

The biotas of the Galápagos Islands are one of the best studied island systems and have provided a broad model for insular species’ origins and evolution. Nevertheless, some locally endemic taxa, such as the Galápagos Rail Laterallus spilonota, remain poorly characterized. Owing to its elusive behavior, cryptic plumage, and restricted distribution, the Galápagos Rail is one of the least studied endemic vertebrates of the Galapagos Islands. To date, there is no genetic data for this species, leaving its origins, relationships to other taxa, and levels of genetic diversity uncharacterized. This lack of information is critical given the adverse fate of island rail species around the world in the recent past. Here, we examine the genetics of Galápagos Rails using a combination of mitogenome de novo assembly with multilocus nuclear and mitochondrial sequencing from both modern and historical samples. We show that the Galápagos Rail is part of the “American black rail clade”, sister to the Black Rail L. jamaicensis, with a colonization of Galápagos dated to 1.2 million years ago. A separate analysis of one nuclear and two mitochondrial markers in the larger population samples demonstrates a shallow population structure across the islands, possibly due to elevated island connectivity. Additionally, birds from the island Pinta possessed the lowest levels of genetic diversity, possibly reflecting past population bottlenecks associated with overgrazing of their habitat by invasive goats. The modern and historical data presented here highlight the low genetic diversity in this endemic rail species and provide useful information to guide conservation efforts.Fil: Chaves, Jaime A.. San Francisco State University; Estados Unidos. Universidad San Francisco de Quito; EcuadorFil: Martinez Torres, Pedro J.. Universidad San Francisco de Quito; EcuadorFil: Depino, Emiliano Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Bio y Geociencias del NOA. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Museo de Ciencias Naturales. Instituto de Bio y Geociencias del NOA; ArgentinaFil: Espinoza Ulloa, Sebastian. University of Saskatchewan; Canadá. Pontificia Universidad Católica del Ecuador; EcuadorFil: García Loor, Jefferson. Universidad San Francisco de Quito; EcuadorFil: Beichman, Annabel C.. University of Washington; Estados UnidosFil: Stervander, Martin. Natural History Museum; Reino Unid

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

Anti-Prion Activity of Brilliant Blue G

BACKGROUND: Prion diseases are fatal neurodegenerative disorders with no effective therapy currently available. Accumulating evidence has implicated over-activation of P2X7 ionotropic purinergic receptor (P2X7R) in the progression of neuronal loss in several neurodegenerative diseases. This has led to the speculation that simultaneous blockade of this receptor and prion replication can be an effective therapeutic strategy for prion diseases. We have focused on Brilliant Blue G (BBG), a well-known P2X7R antagonist, possessing a chemical structure expected to confer anti-prion activity and examined its inhibitory effect on the accumulation of pathogenic isoforms of prion protein (PrPres) in a cellular and a mouse model of prion disease in order to determine its therapeutic potential. PRINCIPAL FINDINGS: BBG prevented PrPres accumulation in infected MG20 microglial and N2a neural cells at 50% inhibitory concentrations of 14.6 and 3.2 µM, respectively. Administration of BBG in vivo also reduced PrPres accumulation in the brains of mice with prion disease. However, it did not appear to alleviate the disease progression compared to the vehicle-treated controls, implying a complex role of P2X7R on the neuronal degeneration in prion diseases. SIGNIFICANCE: These results provide novel insights into the pathophysiology of prion diseases and have important implications for the treatment

Trazodone regulates neurotrophic/growth factors, mitogen-activated protein kinases and lactate release in human primary astrocytes

Background: In the central nervous system, glial cells provide metabolic and trophic support to neurons and respond to protracted stress and insults by up-regulating inflammatory processes. Reactive astrocytes and microglia are associated with the pathophysiology of neuronal injury, neurodegenerative diseases and major depression, in both animal models and human brains. Several studies have reported clear anti-inflammatory effects of anti-depressant treatment on astrocytes, especially in models of neurological disorders. Trazodone (TDZ) is a triazolopyridine derivative that is structurally unrelated to other major classes of antidepressants. Although the molecular mechanisms of TDZ in neurons have been investigated, it is unclear whether astrocytes are also a TDZ target. Methods: The effects of TDZ on human astrocytes were investigated in physiological conditions and following inflammatory insult with lipopolysaccharide (LPS) and tumour necrosis factor-aα (TNF-aα). Astrocytes were assessed for their responses to pro-inflammatory mediators and cytokines, and the receptors and signalling pathways involved in TDZ-mediated effects were evaluated. Results: TDZ had no effect on cell proliferation, but it decreased pro-inflammatory mediator release and modulated trophic and transcription factor mRNA expression. Following TDZ treatment, the AKT pathway was activated, whereas extracellular signal-regulated kinase and c-Jun NH2-terminal kinase were inhibited. Most importantly, a 72-h TDZ pre-treatment before inflammatory insult completely reversed the anti-proliferative effects induced by LPS-TNF-aα. The expression or the activity of inflammatory mediators, including interleukin-6, c-Jun NH2-terminal kinase and nuclear factor ΚB, were also reduced. Furthermore, TDZ affected astrocyte metabolic support to neurons by counteracting the inflammation-mediated lactate decrease. Finally, TDZ protected neuronal-like cells against neurotoxicity mediated by activated astrocytes. These effects mainly involved an activation of 5-HT1A and an antagonism at 5-HT2A/C serotonin receptors. Fluoxetine, used in parallel, showed similar final effects nevertheless it activates different receptors/intracellular pathways. Conclusions: Altogether, our results demonstrated that TDZ directly acts on astrocytes by regulating intracellular signalling pathways and increasing specific astrocyte-derived neurotrophic factor expression and lactate release. TDZ may contribute to neuronal support by normalizing trophic and metabolic support during neuroinflammation, which is associated with neurological diseases, including major depression

Functional effects of the chronic expression of IL-1 beta in the striatum

Interleukin-1 beta (IL-1) is associated with a spectrum of inflammatory processes related to neurodegenerative disease. The effects of single-bolus injections of IL-1 into the CNS parenchyma give rise to neutrophil (PMN) recruitment, transient blood–brain barrier (BBB) breakdown, but no overt damage to CNS integrity. The effects of long-term IL-1 expression in brain parenchyma on CNS integrity have not been investigated. We used a recombinant adenovirus expressing IL-1 (AdIL-1) to examine the chronic effects of IL-1 expression in the CNS. Histochemical and immunohistochemical methods were used to characterize the immune response to an intrastriatal injection of 107 pfu of AdIL-1 and ELISA to quantified the IL-1 protein produced by the adenovector. IL-1 expression was detectable at 4, 8, 14, and 30 days postinjection. At days 1 and 2, some monocyte adherence was observed in the lumen of the vessels but between days 8 and 14 there was marked and restricted recruitment of PMNs, vasodilatation and breakdown of the BBB. Microglia and astrocyte activation was evident at days 2, 8 and 14. At days 8 and 14, disorganization of the nervous tissue, demyelination were observed. The number of neurons in the striatum was not affected by the treatment. At 30 days, the nervous tissue appeared normal with no signs of demyelination, infiltration or BBB breakdown. Thus, we show that chronic expression of IL-1 can damage CNS integrity, that IL-1 generates a restricted leukocyte recruitment profile in the CNS, and that there is no tachyphylaxis to chronic IL-1 expression<br/