Mitochondrial Superoxide Contributes to Blood Flow and Axonal Transport Deficits in the Tg2576 Mouse Model of Alzheimer's Disease

Alzheimer's disease (AD) is a neurodegenerative disease characterized by the progressive decline in cognitive functions and the deposition of aggregated amyloid beta (Abeta) into senile plaques and the protein tau into tangles. In addition, a general state of oxidation has long been known to be a major hallmark of the disease. What is not known however, are the mechanisms by which oxidative stress contributes to the pathology of AD.In the current study, we used a mouse model of AD and genetically boosted its ability to quench free radicals of specific mitochondrial origin. We found that such manipulation conferred to the AD mice protection against vascular as well as neuronal deficits that typically affect them. We also found that the vascular deficits are improved via antioxidant modulation of the endothelial nitric oxide synthase, an enzyme primarily responsible for the production of nitric oxide, while neuronal deficits are improved via modulation of the phosphorylation status of the protein tau, which is a neuronal cytoskeletal stabilizer.These findings directly link free radicals of specific mitochondrial origin to AD-associated vascular and neuronal pathology

Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence

About one-third of people with major depressive disorder (MDD) fail at least two antidepressant drug trials at 1 year. Together with clinical and experimental evidence indicating that the pathophysiology of MDD is multifactorial, this observation underscores the importance of elucidating mechanisms beyond monoaminergic dysregulation that can contribute to the genesis and persistence of MDD. Oxidative stress and neuroinflammation are mechanistically linked to the presence of neurovascular dysfunction with blood-brain barrier (BBB) hyperpermeability in selected neurological disorders, such as stroke, epilepsy, multiple sclerosis, traumatic brain injury, and Alzheimer’s disease. In contrast to other major psychiatric disorders, MDD is frequently comorbid with such neurological disorders and constitutes an independent risk factor for morbidity and mortality in disorders characterized by vascular endothelial dysfunction (cardiovascular disease and diabetes mellitus). Oxidative stress and neuroinflammation are implicated in the neurobiology of MDD. More recent evidence links neurovascular dysfunction with BBB hyperpermeability to MDD without neurological comorbidity. We review this emerging literature and present a theoretical integration between these abnormalities to those involving oxidative stress and neuroinflammation in MDD. We discuss our hypothesis that alterations in endothelial nitric oxide levels and endothelial nitric oxide synthase uncoupling are central mechanistic links in this regard. Understanding the contribution of neurovascular dysfunction with BBB hyperpermeability to the pathophysiology of MDD may help to identify novel therapeutic and preventative approaches

Nanotubes for Biotechnology

Overall, nanotubes are a fascinating and novel class of materials which have improved areas of biotechnology. Nanotubes will almost certainly have an integral part to play in healthcare and biotechnology within the coming decade and the ..

Nanotubes for Biotechnology

Overall, nanotubes are a fascinating and novel class of materials which have improved areas of biotechnology. Nanotubes will almost certainly have an integral part to play in healthcare and biotechnology within the coming decade and the ..

Dielectrophoresis of poly at and poly GC DNA Nanomanipulation

Dielectrophoresis (DEP) is the induced motion of polarizable particles in non-uniform electric fields. Used for many years for the manipulation of particles from cell-scale to macromolecules, we present here the application of the technique for manipulation of DNA containing only adenine-thymine (poly AT) bases, and that of DNA containing only cytosine-guanine (poly GC), using microfabricated electrode structures. Poly AT was stained with DAPI and JOJO-1 for poly GC DNA. It was found that there were differences between the frequency-dependent DEP behavior of the two molecules; when looking at the difference between the two types on crossover frequency (the point where DEP changes from attractive to repulsive), it was found that they varied by up to a factor of 2. This points to possible insigns in the charge conduction mechanism in different DNA forms, as well as potential new mechanisms for gene separations and sequencing. © 2012 IEEE

Dielectrophoresis of poly at and poly GC DNA Nanomanipulation

Dielectrophoresis (DEP) is the induced motion of polarizable particles in non-uniform electric fields. Used for many years for the manipulation of particles from cell-scale to macromolecules, we present here the application of the technique for manipulation of DNA containing only adenine-thymine (poly AT) bases, and that of DNA containing only cytosine-guanine (poly GC), using microfabricated electrode structures. Poly AT was stained with DAPI and JOJO-1 for poly GC DNA. It was found that there were differences between the frequency-dependent DEP behavior of the two molecules; when looking at the difference between the two types on crossover frequency (the point where DEP changes from attractive to repulsive), it was found that they varied by up to a factor of 2. This points to possible insigns in the charge conduction mechanism in different DNA forms, as well as potential new mechanisms for gene separations and sequencing. © 2012 IEEE

Investigation of gold nanoparticle radiosensitisation mechanisms using a free radical scavenger and protons of different energies

Gold nanoparticles (GNPs) have been shown to sensitise cancer cells to X-ray radiation, particularly at kV energies where photoelectric interactions dominate and the high atomic number of gold makes a large difference to X-ray absorption. Protons have a high cross-section for gold at a large range of relevant clinical energies, and so potentially could be used with GNPs for increased therapeutic effect. Here, we investigate the contribution of secondary electron emission to cancer cell radiosensitisation and investigate how this parameter is affected by proton energy and a free radical scavenger. We simulate the emission from a realistic cell phantom containing GNPs after traversal by protons and X-rays with different energies. We find that with a range of proton energies (1 -250 MeV) there is a small increase in secondaries compared to a much larger increase with X-rays. Secondary electrons are known to produce toxic free radicals. Using a cancer cell line in vitro we find that a free radical scavenger has no protective effect on cells containing GNPs irradiated with 3 MeV protons, while it does protect against cells irradiated with X-rays