A botanical extract (Regrapex-R) prepared from whole grape (Vitis vinifera) and Polygonum cuspidatum, which contains polyphenols, including flavans, anthocyanins, emodin, and resveratrol, exhibited dose-dependent scavenging effects on reactive oxygen species (ROS). The extract inhibited increases of ROS and protein carbonyl in isolated rat liver mitochondria following exposure to 2,2'-azobis (2-amidino propane) dihydrocholoride (AAPH), a potent lipid oxidant generator.
Amyotrophic lateral sclerosis (ALS) is a fatal motoneuron disease with no current effective treatment. Accumulation of abnormal protein inclusions containing SOD1, TARDBP, FUS, among other proteins, is a pathological hallmark of ALS. Autophagy is the major degradation pathway involved in the clearance of damaged organelles and protein aggregates. Although autophagy has been shown to efficiently degrade ALS-linked mutant protein in cell culture models, several studies suggest that autophagy impairment may also contribute to disease pathogenesis.
BACKGROUND AND AIMS: The primary purpose of the present study was to investigate the effects of 10, 25, and 40% dietary restriction (DR) on non-neoplastic diseases in rodents at 58 and 110 weeks of age, and to determine whether low-level DR (10 and 25%) can increase the survival rate and decrease variability in chronic bioassay studies.
Journal of Toxicology and Environmental Health. Part A
The use of dietary adsorbents to reduce arsenic (As) exposure is innovative. Ferrihydrite successfully sorbs arsenite and asenate over a wide range of pH conditions and the As-ferrihydrite complexes are stable in gastrointestinal (GIT) models.
OBJECTIVE: To observe the effect of prolonged feeding of dietary nucleotides (NTs), and to clarify the effect of NTs on life extension of Sprague-Dawley rats. METHODS: There were 50 Sprague-Dawley rats in each group (male:female ratio=1:1), which were fed diets supplemented with NTs at concentrations of 0%, 0.01%, 0.04%, 0.16% and 0.64% (wt/wt) from the age of 4 weeks until natural death. We investigated the moribundity and mortality, survival time, spontaneous tumor incidence, and serum oxidative status.
Glutamate is the major excitatory neurotransmitter in the CNS that is cleared from the extracellular space by a family of high-affinity glutamate transporters. The astroglial glutamate transporter EAAT2 is thought to carry out the uptake of the vast quantity of glutamate, and dysregulation of EAAT2 expression is involved in the pathogenesis of neurological disorders with marked excitotoxic components. Here, we present a novel epigenetic mechanism by which the human EAAT2 gene is kept in a silent state. Sequence inspection identified a classical CpG island at the EAAT2 promoter.
BACKGROUND: Current pharmacological treatments for schizophrenia target G protein-coupled receptors (GPCRs), including dopamine receptors. Ligand-bound GPCRs are regulated by a family of G protein-coupled receptor kinases (GRKs), members of which uncouple the receptor from heterotrimeric G proteins, desensitize the receptor, and induce receptor internalization via the arrestin family of scaffolding and signaling molecules.
BACKGROUND: Although there is indirect evidence that the effects of antipsychotic drugs may involve modulation of dopamine transmission, their mechanism of action is poorly understood. We hypothesized that antipsychotic drugs mediate their effects by epigenetic modulation. Here, we tested the effect of an antipsychotic, olanzapine, on the DNA methylation status of genes following chronic treatment using rat-specific methylation arrays.
Brain-derived neurotrophic factor (BDNF) has a crucial role in modulating neural and behavioral plasticity to drugs of abuse. We found a persistent downregulation of exon-specific Bdnf expression in the ventral tegmental area (VTA) in response to chronic opiate exposure, which was mediated by specific epigenetic modifications at the corresponding Bdnf gene promoters.
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience
Epigenetic processes that regulate histone acetylation play an essential role in behavioral and molecular responses to cocaine. To date, however, only a small fraction of the mechanisms involved in the addiction-associated acetylome have been investigated. Members of the bromodomain and extraterminal (BET) family of epigenetic "reader" proteins (BRD2, BRD3, BRD4, and BRDT) bind acetylated histones and serve as a scaffold for the recruitment of macromolecular complexes to modify chromatin accessibility and transcriptional activity.