APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size.

The E4 variant of APOE strongly predisposes individuals to late-onset Alzheimer's disease. We demonstrate that in response to lipogenesis, apolipoprotein E (APOE) in astrocytes can avoid translocation into the endoplasmic reticulum (ER) lumen and traffic to lipid droplets (LDs) via membrane bridges at ER-LD contacts. APOE knockdown promotes fewer, larger LDs after a fatty acid pulse, which contain more unsaturated triglyceride after fatty acid pulse-chase.

Contact-FP: A Dimerization-Dependent Fluorescent Protein Toolkit for Visualizing Membrane Contact Site Dynamics.

Membrane contact sites (MCSs) are sites of close apposition between two organelles used to exchange ions, lipids, and information. Cells respond to changing environmental or developmental conditions by modulating the number, extent, or duration of MCSs. Because of their small size and dynamic nature, tools to study the dynamics of MCSs in live cells have been limited.

Sex differences in long-term behavioral alterations, especially anxiety, following prenatal fluoxetine exposure in C57BL/6 mice.

Evidence demonstrates that psychiatric disorders during pregnancy are detrimental to the offspring. Many disorders are treated with SSRIs and increasing numbers of pregnant women now receive these drugs during gestation. The long-term neurobehavioral consequences of prenatal SSRI exposure require further evaluation.

Neuropsychological Change After a Single Season of Head Impact Exposure in Youth Football.

Objectives: Head impact exposure (HIE) in youth football is a public health concern. The objective of this study was to determine if one season of HIE in youth football was related to cognitive changes.

Method: Over 200 participants (ages 9-13) wore instrumented helmets for practices and games to measure the amount of HIE sustained over one season.

Psychometric properties of the standardized assessment of concussion in youth football: Validity, reliability, and demographic factors.

The objective of this study was to determine the psychometrics (reliability, validity) of the original Standardized Assessment of Concussion (SAC) in a youth sample (ages 11 to 13). Demographic factors of race, level of vocabulary knowledge, mother's level of education were also considered. Over 150 youth football athletes completed the SAC and a brief battery of NIH Toolbox cognitive tests as part of a larger study on biomechanical factors in youth sport concussion.

Genome-wide In Vivo CNS Screening Identifies Genes that Modify CNS Neuronal Survival and mHTT Toxicity.

Unbiased in vivo genome-wide genetic screening is a powerful approach to elucidate new molecular mechanisms, but such screening has not been possible to perform in the mammalian central nervous system (CNS). Here, we report the results of the first genome-wide genetic screens in the CNS using both short hairpin RNA (shRNA) and CRISPR libraries. Our screens identify many classes of CNS neuronal essential genes and demonstrate that CNS neurons are particularly sensitive not only to perturbations to synaptic processes but also autophagy, proteostasis, mRNA processing, and mitochondrial function.

E46K-like α-synuclein mutants increase lipid interactions and disrupt membrane selectivity.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders, and both genetic and histopathological evidence have implicated the ubiquitous presynaptic protein α-synuclein (αSyn) in its pathogenesis. Recent work has investigated how disrupting αSyn's interaction with membranes triggers trafficking defects, cellular stress, and apoptosis. Special interest has been devoted to a series of mutants exacerbating the effects of the E46K mutation (associated with autosomal dominant PD) through homologous Glu-to-Lys substitutions in αSyn's N-terminal region ( E35K and E61K).

Expression and Purification of Untagged α-Synuclein.

α-Synuclein (αS) is an abundant neuronal protein which has been implicated, among others, in the pathogenesis of neurodegenerative diseases like Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In fact, αS is the major constituent of Lewy bodies, the primarily proteinaceous inclusions found in the nervous tissue of PD and DLB patients. While its physiological role is unclear, it is believed to be involved in the regulation of synaptic vesicle exocytosis.

pTSara-NatB, an improved N-terminal acetylation system for recombinant protein expression in E. coli.

N-terminal acetylation is one of the most common co- and post-translational modifications of the eukaryotic proteome and regulates numerous aspects of cellular physiology, such as protein folding, localization and turnover. In particular α-synuclein, whose dyshomeostasis has been tied to the pathogenesis of several neurodegenerative disorders, is completely Nα-acetylated in nervous tissue. In this work, building on previous reports, we develop and characterize a bacterial N-terminal acetylation system based on the expression of the yeast N-terminal acetyltransferase B (NatB) complex under the control of the PBAD (L-arabinose-inducible) promoter.

Single Season Changes in Resting State Network Power and the Connectivity between Regions: Distinguish Head Impact Exposure Level in High School and Youth Football Players.

The effect of repetitive sub-concussive head impact exposure in contact sports like American football on brain health is poorly understood, especially in the understudied populations of youth and high school players. These players, aged 9-18 years old may be particularly susceptible to impact exposure as their brains are undergoing rapid maturation. This study helps fill the void by quantifying the association between head impact exposure and functional connectivity, an important aspect of brain health measurable via resting-state fMRI (rs-fMRI).

Inter-Rater Reliability of Preprocessing EEG Data: Impact of Subjective Artifact Removal on Associative Memory Task ERP Results.

The processing of EEG data routinely involves subjective removal of artifacts during a preprocessing stage. Preprocessing inter-rater reliability (IRR) and how differences in preprocessing may affect outcomes of primary event-related potential (ERP) analyses has not been previously assessed. Three raters independently preprocessed EEG data of 16 cognitively healthy adult participants (ages 18-39 years) who performed a memory task.

Complete versus anterior two-thirds corpus callosotomy in children: analysis of outcome.

Object: The goal of this study was to evaluate the efficacy of anterior versus complete sectioning of the corpus callosum in children suffering from medically refractory epilepsy. The authors report seizure outcome in patients who underwent anterior two-thirds or complete corpus callosotomy (CC) during the period 1995-2008 at St. Louis Children's Hospital.