Stroke, an age-related disorder involving degeneration of neurons resulting from cerebral ischemia, is a major cause disability and mortality. Although dietary restriction (DR) extends lifespan reduces levels cellular oxidative stress in several different organ systems including the brain, impact DR on ischemic brain injury unknown. We report that maintenance adult rats regimen resulted reduced damage improved behavioral outcome middle artery occlusion-reperfusion (MCAO-R) stroke model....

Abstract: The β‐amyloid precursor protein (βAPP) is the source of amyloid β‐peptide that accumulates in brain Alzheimer's disease. A major processing pathway for βAPP involves an enzymatic cleavage within sequence liberates secreted forms (APP S s) into extracellular milieu. We now report postischemic administration these APP s intracerebroventricularly protects neurons CA1 region rat hippocampus against ischemic injury. Treatment with 695 or 751 resulted increased neuronal survival, and...

The bcl-2 protooncogene product possesses antiapoptotic properties in neuronal and nonneuronal cells. Recent data suggest that Bcl-2's potency as a survival factor hinges on its ability to suppress oxidative stress, but neither the subcellular site(s) nor mechanism of action is known. In this report electron paramagnetic resonance (EPR) spectroscopy analyses were used investigate local effects Bcl-2 membrane lipid peroxidation. Using hydrogen peroxide (H2O2) amyloid beta-peptide (A beta)...

Dietary restriction (DR; reduced calorie intake) increases the lifespan of rodents and their resistance to cancer, diabetes other age-related diseases. DR also exerts beneficial effects on brain including enhanced learning memory increased neurons excitotoxic, oxidative metabolic insults. The mechanisms underlying neuronal plasticity survival are unknown. In present study we show that levels brain-derived neurotrophic factor (BDNF) significantly in hippocampus, cerebral cortex striatum mice...

The catalytic subunit of telomerase (TERT) is a specialized reverse transcriptase that has been associated with cell immortalization and cancer. It was reported recently TERT expressed in neurons throughout the brain embryonic early postnatal development, but absent from adult brain. We now report suppression levels function mouse hippocampal culture using antisense technology inhibitor 3' -azido-2' -dideoxythymidine significantly increases their vulnerability to death induced by amyloid...

Synapse loss, deposits of amyloid β-peptide (Aβ), impaired energy metabolism, and cognitive deficits are defining features Alzheimer's disease (AD). Estrogen replacement therapy reduces the risk developing AD in postmenopausal women. Because synapses likely sites for initiation neurodegenerative cascades AD, we tested hypothesis that estrogens act directly on to suppress oxidative impairment membrane transport systems. Exposure rat cortical synaptosomes Aβ25-35 (Aβ) FeSO4 induced lipid...

Alzheimer's disease is characterized by amyloid beta-peptide deposition, synapse loss, and neuronal death, which are correlated with cognitive impairments. Mutations in the presenilin-1 gene on chromosome 14 causally linked to many cases of early-onset inherited disease. We report that synaptosomes prepared from transgenic mice harboring mutations exhibit enhanced elevations cytoplasmic calcium levels following exposure depolarizing agents, beta-peptide, a mitochondrial toxin compared...

Apolipoprotein E (apoE)-related synthetic peptides, the 22 kDa N-terminal thrombin-cleavage fragment of apoE (truncated apoE), and full-length have all been shown to exhibit neurotoxic activity under certain culture conditions. In present study, protease inhibitors reduced neurotoxicity proteolysis but did not block toxicity truncated or a peptide, suggesting that fragments may account for its toxicity. Additional experiments demonstrated both peptide elicit an increase in intracellular...

Integrins are integral membrane proteins that mediate adhesive interactions of cells with the extracellular matrix and other cells. Integrin engagement results in activation intracellular signaling cascades effect several different cellular responses including motility, proliferation survival. Although integrins known to provide cell survival various types non-neuronal cells, possibility modulate neuron has not been explored. We now report data demonstrating a neuroprotective function...

Abstract Environmental chemicals, such as polychlorinated biphenyls (PCBs), may be atherogenic by disrupting normal functions of the vascular endothelium. To investigate this hypothesis, porcine pulmonary artery‐derived endothelial cells were exposed to 3,3′,4,4′‐tetrachlorobiphenyl (PCB 77), 2,3,4,4′,5‐pentachlorobiphenyl 114), or 2,2′,4,4′,5,5′‐hexachlorobiphenyl 153) for up 24 hours. These PCBs selected their varying binding avidities with aryl hydrocarbon (Ah) receptor and differences in...

Activation of ionotropic glutamate receptors the AMPA and NMDA subtypes likely contributes to neuronal injury death in various neurodegenerative disorders. Excitotoxicity can manifest as either apoptosis or necrosis, but mechanisms that determine mode cell are not known. We now report levels receptor subunits GluR-1 GluR-4 rapidly decreased cultured rat hippocampal neurons undergoing response withdrawal trophic support (WTS), whereas NR1, NR2A, NR2B unchanged. Exposure isolated synaptosomal...

MUTATIONS in presenilin-1 (PS-1) account for approximately half the cases of autosomal dominant early-onset Alzheimer's disease (AD). Recent data indicate that PS-1 mutations may render neurons vulnerable to apoptosis induced by various insults. We now report 17β-estradiol, which appears reduce risk sporadic AD, protects cultured PC12 cells expressing mutant against trophic factor withdrawal (TFW) and exposure amyloid β-peptide 25–35 (Aβ). Estriol also provided significant protection TFW Aβ,...

Lipolytic products of triglyceride-rich lipoproteins, i.e., free fatty acids, may cause activation and dysfunction the vascular endothelium. Mechanisms these effects include lipid peroxidation. One major biologically active peroxidation n-6 such as linoleic acid or arachidonic acid, is aldehyde 4-hydroxynonenal (HNE). To study hypothesis that HNE be a critical factor in endothelial cell caused by human umbilical cells (HUVEC) were treated with up to160 μM acid. formation was detected...

Abstract : Recent studies have shown that rats and mice maintained on a dietary restriction (DR) regimen exhibit increased resistance of neurons to excitotoxic, oxidative, metabolic insults in experimental models Alzheimer's, Parkinson's, Huntington's diseases stroke. Because synaptic terminals are sites where the neurodegenerative process may begin such disorders, we determined effects DR homeostasis vulnerability oxidative insults. Basal levels glucose uptake were similar cerebral cortical...

Hydrolysis of membrane phospholipids spinal cord neurons is one the first events initiated in trauma. In this process, free fatty acids, and particular arachidonic acid, are released. Exposure to acid can compromise cell survival initiate apoptotic death. order determine potential mechanisms apoptosis induced by activation caspases ‐3, ‐8, ‐9, as well release cytochrome c into cytoplasm were measured cultured exposed 10 µ m acid. addition, because nicotine exert a variety neuroprotective...