Biology subjects

Paez, D.

Publications and source records attributed to Paez, D..

2 recordsLinked to original sources

bioRxiv2024

Impaired 26S proteasome causes leaning and memory deficiency and induces neuroinflammation mediated by NF-kappaB in mice

A reduction in proteasome activity, loss of synapses, and increased neuroinflammation in the brain are hallmarks of aging and many neurodegenerative disorders, including Alzheimers disease (AD); however, whether proteasome dysfunction is causative to neuroinflammation remains less understood. In this study, we investigated the impact of 26S proteasome deficiency on neuroinflammation in the Psmc1 knockout (KO) mice deficient in a 19S proteasome subunit limited to the forebrain region. Our results revealed that impaired 26S proteasome causes reduced learning and memory capability and overt neuroinflammation in the Psmc1 KO brain at eight weeks of age. Pronounced neuroinflammation was confirmed by increased levels of several key immune response-related proteins, including Stat1, Trem2, and NF-{kappa}B, and by activation of astrocytes and microglia in the KO brain. To validate NF-{kappa}B mediating neuroinflammation, we administered a selective NF-{kappa}B inhibitor to the KO animals, and following the treatment, the KO mice exhibited improved learning and memory behaviors and reduced neuroinflammation compared to the control animals. These data indicate that impaired 26S proteasome causes AD-like cognitive deficiency and induces neuroinflammation mediated largely by NF-{kappa}B. These results may aid the development of effective therapeutics for AD and other neurodegenerative disorders where impaired proteasome activity is consistently coupled with neuroinflammation.

neuroscience↗

bioRxiv2016

Eco-evolutionary theory and insect outbreaks

Eco-evolutionary theory argues that population cycles in consumer-resource interactions are partly driven by natural selection, such that changes in densities and changes in trait values are mutually reinforcing. Evidence that this theory explains cycles in nature, however, is almost nonexistent. Experimental tests of model predictions are almost always impossible because of the long time scales over which cycles occur, but for most organisms, even tests of model assumptions are logistically impractical. For insect baculoviruses in contrast, tests of model assumptions are straightforward, and baculoviruses often drive outbreaks of forest-defoliating insects, as in the gypsy moth that we study here. We therefore used field experiments with the gypsy moth baculovirus to test two key assumptions of eco-evolutionary models of host-pathogen population cycles, that reduced host infection risk is heritable and costly. Our experiments confirm the two assumptions, and inserting parameters estimated from our data into the models gives cycles closely resembling gypsy moth outbreak cycles in North America, whereas standard models predict unrealistic stable equilibria. Our work shows that eco-evolutionary models are useful for explaining outbreaks of forest insect defoliators, while widespread observations of intense selection imposed by natural enemies on defoliators, and frequent laboratory observations of heritable and costly resistance in defoliators, suggest that eco-evolutionary dynamics may play a general role in defoliator outbreaks.

ecology↗