In both cases, an inverted-U-shaped VE-822 mouse dose-effect function was observed, with lower doses improving recognition but higher doses having no effect. We then examined the effects of CDPPB (0, 3, 10, or 30 mg/kg) on markers of synaptic plasticity in prefrontal cortex and hippocampus, focusing on the expression and phosphorylation status of proteins involved in NMDA related signaling, including the NMDA receptor subunits NR1 and NR2B, the AMPA receptor subunit GluR1, alpha Ca((2+))/CaM dependent Ser-Thr kinases II (alpha
CaMKII), and the transcription factor CREB. Expression and phosphorylation of many of these proteins, particularly in the prefrontal cortex, were also characterized by an inverted-U-shaped dose-effect function. Taken together, these findings show that mGluR5 activation enhances NMDA receptor function and markers of DihydrotestosteroneDHT supplier neuronal plasticity commensurate with improvements in recognition
memory. However, the effects of CDPPB are heavily dependent on dose, with higher doses being ineffective in improving recognition memory and producing downstream effects consistent with heightened NMDA receptor activation. These findings may have important implications for the development of mGluR5 PAMs to treat schizophrenia. (C) 2009 Elsevier Ltd. All rights reserved.”
“Spatially structured ecological interactions can shape selection pressures experienced by a population’s different phenotypes. We study spatial competition between phenotypes subject to antagonistic pleiotropy between reproductive effort and mortality rate. The constraint we invoke reflects a previous life-history analysis; the implied dependence STI571 indicates that although propagation and mortality rates both vary, their ratio is fixed. We develop a stochastic invasion
approximation predicting that phenotypes with higher propagation rates will invade an empty environment (no biotic resistance) faster, despite their higher mortality rate. However, once population density approaches demographic equilibrium, phenotypes with lower mortality are favored, despite their lower propagation rate. We conducted a set of pairwise invasion analyses by simulating an individual-based model of preemptive competition. In each case, the phenotype with the lowest mortality rate and (via antagonistic pleiotropy) the lowest propagation rate qualified as evolutionarily stable among strategies simulated. This result, for a fixed propagation to mortality ratio, Suggests that a selective response to spatial competition can extend the time scale of the population’s dynamics, which in turn decelerates phenotypic evolution. (c) 2009 Elsevier Ltd. All rights reserved.”
“Neurofibrillary tangles composed of hyperphosphorylated tau are a major hallmark of Alzheimer’s Disease. This phosphorylated tau may be a root cause of the disorder and therefore understanding its regulation is important for therapeutic intervention.