Plasma phospholipids identify antecedent memory impairment in older adults.

Alzheimer's disease causes a progressive dementia that currently affects over 35 million individuals worldwide and is expected to affect 115 million by 2050 (ref. 1). There are no cures or disease-modifying therapies, and this may be due to our inability to detect the disease before it has progressed to produce evident memory loss and functional decline.

Expression of Voltage-Gated Sodium Channel Na1.8 in Human Prostate Cancer is Associated with High Histological Grade.

Voltage-gated sodium (Na) channels are required for impulse conductance in excitable tissues. Nas have been linked to human cancers, including prostate. The expression and distribution of Na isoforms (Na1.

Network modeling to identify new mechanisms and therapeutic targets for Parkinson's disease.

Biomolecules in subnetworks are the focus of a new strategy to develop drugs that halt complex diseases. In this article, the authors use genome-wide association study and linkage data derived from Parkinson's disease studies to illustrate how algorithms that use gene and protein interaction databases reveal subnetworks in biological systems that suggest mechanisms for disease progression. Network modeling may help develop testable hypotheses for neurodegenerative diseases and open up new avenues for therapeutic development.

Synthesis and biological evaluation of a fluorescent analog of phenytoin as a potential inhibitor of neuropathic pain and imaging agent.

Here we report on a novel fluorescent analog of phenytoin as a potential inhibitor of neuropathic pain with potential use as an imaging agent. Compound 2 incorporated a heptyl side chain and dansyl moiety onto the parent compound phenytoin and produced greater displacement of BTX from sodium channels and greater functional blockade with greatly reduced toxicity. Compound 2 reduced mechano-allodynia in a rat model of neuropathic pain and was visualized ex vivo in sensory neuron axons with two-photon microscopy.

Delayed rehabilitation with task-specific therapies improves forelimb function after a cervical spinal cord injury.

Purpose: The effect of activity based therapies on restoring forelimb function in rats was evaluated when initiated one month after a cervical spinal cord injury.

Methods: Adult rats received a unilateral over-hemisection of the spinal cord at C4/5, which interrupts the right side of the spinal cord and the dorsal columns bilaterally, resulting in severe impairments in forelimb function with greater impairment on the right side. One month after injury rats were housed in enriched housing and received daily training in reaching, gridwalk, and CatWalk.

Synthesis and evaluation of hermitamides A and B as human voltage-gated sodium channel blockers.

Hermitamides A and B are lipopeptides isolated from a Papau New Guinea collection of the marine cyanobacterium Lyngbya majuscula. We hypothesized that the hermitamides are ligands for the human voltage-gated sodium channel (hNa(V)) based on their structural similarity to the jamaicamides. Herein, we describe the nonracemic total synthesis of hermitamides A and B and their epimers.

Quantitative analysis of the heteromeric neuronal nicotinic receptors in the rat hippocampus.

The objective of this study was to identify and quantify the heteromeric neuronal nicotinic receptors (nAChRs) in the rat hippocampus. The density of nAChR subtypes was assessed by labeling them with [(3)H]epibatidine ([(3)H]EB) followed by immunoprecipitation with subunit-selective antibodies. Sequential immunoprecipitation assays were used to establish associations between two different subunits, which then allowed the full subunit composition of the receptors to be deduced.

Activity-based therapies to promote forelimb use after a cervical spinal cord injury.

Significant interest exists in strategies for improving forelimb function following spinal cord injury. We investigated the effect of enriched housing combined with skilled training on the recovery of skilled and automatic forelimb function after a cervical spinal cord injury in adult rats. All animals were pretrained in skilled reaching, gridwalk crossing, and overground locomotion.

Retrograde and anterograde transport of HIV protein gp120 in the nervous system.

Neurodegeneration and gliosis are prominent pathological features of subjects with human immunodeficiency virus (HIV) dementia complex (HAD). In these patients, neurodegeneration occurs in uninfected neurons. In addition, these patients develop sensory neuropathy despite the antiretroviral therapy.

Delayed intervention with transplants and neurotrophic factors supports recovery of forelimb function after cervical spinal cord injury in adult rats.

The adult central nervous system is capable of considerable anatomical reorganization and functional recovery after injury. Functional outcomes, however, vary greatly, depending upon size and location of injury, type and timing of intervention, and type of recovery and plasticity evaluated. The present study was undertaken to assess the recovery of skilled and unskilled forelimb function in adult rats after a C5/C6 spinal cord over-hemisection and delayed intervention with fetal spinal cord transplants and neurotrophins.

Differences in cytokine gene expression profile between acute and secondary injury in adult rat spinal cord.

It is likely that the environment within the injured spinal cord influences the capacity of fetal spinal cord transplants to support axonal growth. We have recently demonstrated that fetal spinal cord transplants and neurotrophin administration support axonal regeneration after spinal cord transection, and that the distance and amount of axonal growth is greater when these treatments are delayed by several weeks after injury. In this study, we sought to determine whether differences in inflammatory mediators exist between the acutely injured spinal cord and the spinal cord after a second injury and re-section, which could provide a more favorable environment for the axonal re-growth.