Library

Notes: l-DOPA is the most effective treatment for Parkinson's disease but in isolated neuronal cultures it is neurotoxic for dopamine (DA) neurones. Experiments in vivo and clinical studies have failed to show toxicity of l-DOPA in animals or patients but that does not exclude the possibility of a toxic effect of l-DOPA on patients with certain genetic risk factors. Mutations of the parkin gene are the most frequent cause of hereditary parkinsonism. Parkin null mice have a mild phenotype that could be modified by different neurotoxins. The aim of this study was to investigate whether the toxic effects of l-DOPA on DA neurones are amplified in parkin null mice. We have measured the effects of l-DOPA on cell viability, tyrosine hydroxylase (TH) expression, DA metabolism and glutathione levels of parkin knockout (PK-KO) midbrain cultures. Neuronal-enriched cultures from PK-KO mice have similar proportions of the different cell types with the exception of a significant increment of microglial cells. l-DOPA (400 µm for 24 h) reduced the number of TH-immunoreactive cells to 50% of baseline and increased twofold the percentage of apoptotic cells in cultures of wild-type (WT) animals. The PK-KO mice, however, are not only resistant to the l-DOPA-induced pro-apoptotic effects but they have an increased number of TH-immunoreactive neurones after treatment with l-DOPA, suggesting that l-DOPA is toxic for neurones of WT mice but not those of parkin null mice. MAPK and phosphatidylinositol-3 kinase signalling pathways are not involved in the differential l-DOPA effects in WT and PK-KO cultures. Intracellular levels of l-DOPA were not different in WT and parkin null mice but the intracellular and extracellular levels of DA and 3-4-dihydroxyphenylacetic acid, however, were significantly increased in parkin null animals. Furthermore, monoamine oxidase activity was significantly increased in parkin null mice, suggesting that these animals have an increased metabolism of DA. The levels of glutathione were further increased in parkin null mice than in controls both with and without treatment with l-DOPA, suggesting that a compensatory mechanism may protect DA neurones from neuronal death. This study opens new avenues for understanding the mechanisms of action of l-DOPA on DA neurones in patients with Park-2 mutations.

Notes: To date, glutathione (GSH) depletion is the earliest biochemical alteration shown in brains of Parkinson's disease patients, but the role of GSH in dopamine cell survival is debated. In this study we show that GSH depletion, produced with GSH synthesis inhibitor, l-buthionine-(S,R)-sulfoximine (BSO), induces selectively neuronal cell death in neuron/glia, but not in neuronal-enriched midbrain cultures and that cell death occurs with characteristics of necrosis and apoptosis. BSO produces a dose- and time-dependent generation of reactive oxygen species (ROS) in neurons. BSO activates extracellular signal-regulated kinases (ERK-1/2), 4 and 6 h after treatment. MEK-1/2 and lipoxygenase (LOX) inhibitors, as well as ascorbic acid, prevent ERK-1/2 activation and neuronal loss, but the inhibition of nitric oxide sintase (NOS), cyclo-oxygenase (COX), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) does not have protective effects. Co-localization studies show that p-ERK-1/2 expression after BSO treatment increased in astrocytes and microglial cells, but not in neurons. Selective metabolic impairment of glial cells with fluoroacetate decreased ERK activation. However, blockade of microglial activation with minocycline did not. Our results indicate that neuronal death induced by GSH depletion is due to ROS-dependent activation of the ERK-1/2 signalling pathway in glial cells. These data may be of relevance in Parkinson's disease, where GSH depletion and glial dysfunction have been documented.

Notes: Nitrogen incorporates into Fe thin films during reactively sputtered TiN capping layer deposition. The influence that this nitrogen incorporation has both on the structure and magnetic properties is discussed for a series of Fe(001) thin films grown at different temperatures. A higher nitrogen content is accompanied by distortion in the Fe lattice and by reduction in the Fe magnetization saturation as well as in the effective anisotropy constant, K. The reduction of K brings as a consequence lowering in the coercive field with respect to equivalent Fe films with no nitrogen present. © 2001 American Institute of Physics.

Notes: We report on a photoluminescence (PL) study on pinholes and their effects on the carrier recombination process in an InGaN/GaN single quantum well sample. By directly imaging the luminescence from the sample, we observed an anisotropic distribution of photogenerated carriers due to diffusion and drift of the carriers near pinholes. The anisotropy, together with micro-PL spectra at different locations near a pinhole, shows evidence of narrowing of the band gap of the quantum well layer near pinholes. The existence of the band gap gradient is confirmed by reflective and photoluminescence images of the sample under global illumination. Possible causes of the band gap gradient include indium concentration inhomogeneity and partial strain relaxation near pinholes. © 2001 American Institute of Physics.

Notes: Electron–phonon interactions in solid C60 have been studied by transient Raman spectroscopy on a picosecond time scale. The electrons were photoinjected into the triply-degenerate states of solid C60 by an ultrashort laser pulse of photon energy (h-dash-bar)ω=2.14 eV. These energetic electrons relax by emitting various phonons. By monitoring the phonon occupations at very low temperatures with anti-Stokes Raman scattering, direct information about the relative strength of the electron–phonon interactions in solid C60 was obtained. Our experimental results demonstrate that electrons interact much more strongly with the low-frequency radial Ag mode than the other phonon modes in solid C60. © 1996 American Institute of Physics.

Notes: We present a study of the infrared absorption and Raman scattering intensity of the local carbon mode in Si1−yCy alloys grown by direct carbon implantation followed by different recrystallization procedures. For the case of laser-induced recrystallization, the integrated infrared absorbances are found to agree with an extrapolation of the calibration curve previously determined for very low substitutional carbon concentrations in Si. We argue that this finding provides strong evidence for the achievement of nearly perfect substitutionality in laser-recrystallized films, even though their carbon concentrations are three orders of magnitude beyond the solubility limit of carbon in Si. This conclusion is found to be consistent with measurements of the intensity of defect-induced Si Raman scattering relative to the Raman intensity of the local carbon mode. The Raman intensity of the local carbon mode at 605 cm−1 relative to the first-order Si Raman line at 521 cm−1 provides an ideal spectroscopic tool for the determination of substitutional carbon concentrations. By correlating Raman and infrared measurements, we find that for laser excitation at 488 nm the intensity ratio is given by I605/I521=(3.7±0.2)ysub. © 1997 American Institute of Physics.

Notes: Polarized off-axis Raman spectroscopy is a technique for measuring the complete tensor nature of stress fields in semiconductors. By combining incident light tilted away from the normal axis with polarization of the incident and scattered beams, any Raman-active optical phonon mode can be selectively studied. Once the frequencies and intensities of these phonons are measured, the complete stress tensor can be uniquely determined. This technique has been applied macroscopically to mechanically deformed silicon wafers under biaxial tension. The results of this approach compare favorably with the stress calculated by means of the theory of elasticity. © 1995 American Institute of Physics.