Effects of Subthalamic Nucleus Lesions and Stimulation upon Corticostriatal Afferents in the 6-Hydroxydopamine-Lesioned Rat

Abnormalities of striatal glutamate neurotransmission may play a role in the pathophysiology of Parkinson's disease and may respond to neurosurgical interventions, specifically stimulation or lesioning of the subthalamic nucleus (STN). The major glutamatergic afferent pathways to the striatum are from the cortex and thalamus, and are thus likely to be sources of striatal neuronally-released glutamate. Corticostriatal terminals can be distinguished within the striatum at the electron microscopic level as their synaptic vesicles contain the vesicular glutamate transporter, VGLUT1. The majority of terminals which are immunolabeled for glutamate but are not VGLUT1 positive are likely to be thalamostriatal afferents. We compared the effects of short term, high frequency, STN stimulation and lesioning in 6-hydroxydopamine (6OHDA)-lesioned rats upon striatal terminals immunolabeled for both presynaptic glutamate and VGLUT1. 6OHDA lesions resulted in a small but significant increase in the proportions of VGLUT1-labeled terminals making synapses on dendritic shafts rather than spines. STN stimulation for one hour, but not STN lesions, increased the proportion of synapses upon spines. The density of presynaptic glutamate immuno-gold labeling was unchanged in both VGLUT1-labeled and -unlabeled terminals in 6OHDA-lesioned rats compared to controls. Rats with 6OHDA lesions+STN stimulation showed a decrease in nerve terminal glutamate immuno-gold labeling in both VGLUT1-labeled and -unlabeled terminals. STN lesions resulted in a significant decrease in the density of presynaptic immuno-gold-labeled glutamate only in VGLUT1-labeled terminals. STN interventions may achieve at least part of their therapeutic effect in PD by normalizing the location of corticostriatal glutamatergic terminals and by altering striatal glutamatergic neurotransmission

XAS STUDY OF SOLUBILIZATION LOCI OF BROMINATED MOLECULES IN AQUEOUS MICELLAR SOLUTIONS

X-ray absorption measurements performed on various systems containing brominated hydrocarbons showed remarkable differences in the bromine K-edge spectra recorded in polar or nonpolar media. For this reason, the brominated hydrocarbons can be used to monitor the polarity of the medium in which they are buried. By determining the coordination of the bromine atom, information on the interactions between the probe molecule and several systems such as micelles, macromolecules, membranes, solvent molecules, and host molecules in inclusion compounds can be obtained. Brominated hydrocarbons in aqueous micellar solutions of sodium and rubidium deoxycholate and sodium dodecyl sulfate have been investigated by means of the XAS technique. Experimental and calculated EXAFS spectra and Fourier transform functions are presented. The results are supported by the XANES experimental spectra. As already found for 2-bromopropane, the polarity of the solubilization loci of bromoethane in sodium and rubidium deoxycholate micellar solutions decreases by increasing the solute concentration. On the contrary, in micellar solutions of sodium dodecyl sulfate, these molecules are embedded in a more apolar environment. The polarity of the spectra of 2-bromopropane changes with the probe concentration, while bromoethane presents a marked apolar coordination which seems to be independent from the probehost ratio. The bromine intermolecular coordination in 1-bromobutane has been found to be apolar in both classes of surfactants. Functionalized surfactants with -ene, -yne, or bromo as the terminal group of the alkyl chain were used by different researchers to investigate micellar structures. In fact, for a micellar aggregate with a hydrocarbon core and an outer region containing the polar heads, the chain terminal group may be buried in the micelle core or placed in the head group region of the micelle, in contact with water. In the latter case, the alkyl chain flexibility may give rise to a chain folded conformation which increases the probability of finding the terminal group at the micelle-water interface. EXAFS data analysis of aqueous micellar solutions of sodium and rubidium 12-bromo dodecyl sulfate and sodium 1 I-bromoundecanoate at the Br K-edge has been accomplished. The chemical constitution of the locus of solubilization of the terminal bromine has been determined, and it has been found to be apolar for the dodecyl sulfate salts and polar in the case of sodium 1 1-bromoundecanoate

XAS characterization of the Zn site of non-structural protein 3 (NS3) from hepatitis C virus

XANES spectra of non structural protein 3 (NS3) have been calculated using 4 Zn coordination models from three crystallographic structures in the Protein Data Base (PDB): 1DY9, subunit B, 1CU1 subunit A and B, and 1JXP subunit B. Results indicate that XANES is an appropriate tool to distinguish among them. Experimental XANES spectra have been simulated refining crystallographic data. The model obtained by XAS is compared with the PDB models. © 2007 American Institute of Physics

In situ XAS studies of the elctrochemical reduction of hydroxocolamin

XAS fluorescence is combined with electrochemical technique to study the reduction of hydroxocobalamin (OH-Co(III)cbl) to cob(II)alamin at the cobalt K-edge. The electrochemical control permits to select a well-defined cobalt oxidation states. The experimental set-up used permits in situ reactions allowing reliable comparison among XANES spectra. The absorption edge shifts to lower energy with the progressive reduction of cobalt. The size of the peak at about 7726 eV (A peak) decrease in Co(II)cbl spectrum. Experimental XANES of OH-Co(ITI)cbl and Co(II)cbl were simulated by multiple scattering theory. Theoretical and experimental data are in agreement, peak intensity being correlated to the coordination number confirming that cobalt is five coordinate in Co(II)cbl sample