Publications by authors named "E Nestler"
The systemic delivery of mRNA molecules to the central nervous system is challenging as they need to cross the blood-brain barrier (BBB) to reach into the brain. Here we design and synthesize 72 BBB-crossing lipids fabricated by conjugating BBB-crossing modules and amino lipids, and use them to assemble BBB-crossing lipid nanoparticles for mRNA delivery. Screening and structure optimization studies resulted in a lead formulation that has substantially higher mRNA delivery efficiency into the brain than those exhibited by FDA-approved lipid nanoparticles.
View Article and Find Full Text PDFThe tools of modern genetics and neurobiology have propelled a renaissance of research that has advanced our understanding of the pathophysiology of drug addiction. We know that an individual's risk for addiction is determined by interactions between genetics and environment and that only a minute fraction of chemical agents share the ability to act on this vulnerability to induce a state of addiction. Repeated exposure to these drugs causes addiction through repeated activation of dopaminergic transmission (and many other actions) in the brain, inducing changes at the molecular, cellular, and synaptic levels that, over time, rewire the circuitry throughout the limbic system.
View Article and Find Full Text PDFBackground: Second-messenger signaling within the mesolimbic reward circuit plays a key role in the negative effects of stress and the underlying mechanisms that promote drug abuse. Because the nucleus accumbens (NAc) integrates reward valence, we investigated how ERK2 (extracellular signal-regulated protein kinase-2) signaling affects the development of stress-related comorbidities, including negative affect and drug sensitivity.
Methods: We assessed how chronic unpredictable stress influenced the phosphorylation of ERK2-signaling proteins within the NAc of male Sprague Dawley rats.