Biomedical subjects

Martine Guillermier

Publications and source records attributed to Martine Guillermier.

5 recordsLinked to original sources

PubMed2006

Synthesis and radiolabeling of N-[4-[4-(2-[11C]methoxyphenyl)piperazin-1-yl]butyl]benzo[b]thiophene-2-carboxamide -- a potential radiotracer for D3 receptor imaging with PET.

FAUC346 (N-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]benzo[b]thiophene-2-carboxamide), an in vitro D(3)-selective ligand, and its normethyl derivative have been synthesized from commercially available 1-(2-substituted-phenyl)piperazines. FAUC346 has been labeled using [(11)C]methyl triflate in acetone containing aqueous NaOH (5 Eq) at -10 degrees C for 1 min, purified on semipreparative reverse-phase high-performance liquid chromatography (HPLC) and formulated as an intravenous injectable solution using a Sep-Pak Plus C(18) device. Up to 5.5 GBq of [(11)C]FAUC346 (N-[4-[4-(2-[methyl-(11)C]methoxyphenyl)piperazin-1-yl]butyl]benzo[b]thiophene-2-carboxamide), with a specific radioactivity of 45-75 GBq/micromol, could be obtained in 30-35 min, including HPLC purification and formulation starting from 44.4 GBq of [(11)C]carbon dioxide. Preliminary pharmacological evaluation of [(11)C]FAUC346 in rat brain clearly demonstrated in vivo selectivity for D(3) receptors and the absence of radiolabeled metabolite within the brain. These encouraging results, however, could not be confirmed in nonhuman primates; therefore, this radioligand does not appear to have the required pharmacological profile for a positron emission tomography probe for imaging D(3) receptors.

Animals↗

PubMed2006

Isoflurane strongly affects the diffusion of intracellular metabolites, as shown by 1H nuclear magnetic resonance spectroscopy of the monkey brain.

Isoflurane is a volatile anesthetic commonly used for animal studies. In particular, diffusion nuclear magnetic resonance (NMR) spectroscopy is frequently performed under isoflurane anesthesia. However, isoflurane is known to affect the phase transition of lipid bilayer, possibly resulting in increased permeability to metabolites. Resulting decreased restriction may affect metabolite apparent diffusion coefficient (ADC). In the present work, the effect of isoflurane dose on metabolite ADC is evaluated using diffusion tensor spectroscopy in the monkey brain. For the five detected intracellular metabolites, the ADC exhibits a significant increase when isoflurane dose varies from 1% to 2%: 13%+/-8% for myo-inositol, 14%+/-13% for total N-acetyl-aspartate, 20%+/-18% for glutamate, 27%+/-7% for total creatine and 53%+/-17% for total choline. Detailed analysis of ADC changes experienced by the five different metabolites argues in favor of facilitated metabolite exchange between subcellular structures at high isoflurane dose. This work strongly supports the idea of metabolite diffusion in vivo being significantly restricted in subcellular structures at long diffusion time, and provides new insights for interpreting ADC values as measured by diffusion NMR spectroscopy.

Anesthetics, Inhalation↗

PubMed2006

Cystamine and cysteamine increase brain levels of BDNF in Huntington disease via HSJ1b and transglutaminase.

There is no treatment for the neurodegenerative disorder Huntington disease (HD). Cystamine is a candidate drug; however, the mechanisms by which it operates remain unclear. We show here that cystamine increases levels of the heat shock DnaJ-containing protein 1b (HSJ1b) that are low in HD patients. HSJ1b inhibits polyQ-huntingtin-induced death of striatal neurons and neuronal dysfunction in Caenorhabditis elegans. This neuroprotective effect involves stimulation of the secretory pathway through formation of clathrin-coated vesicles containing brain-derived neurotrophic factor (BDNF). Cystamine increases BDNF secretion from the Golgi region that is blocked by reducing HSJ1b levels or by overexpressing transglutaminase. We demonstrate that cysteamine, the FDA-approved reduced form of cystamine, is neuroprotective in HD mice by increasing BDNF levels in brain. Finally, cysteamine increases serum levels of BDNF in mouse and primate models of HD. Therefore, cysteamine is a potential treatment for HD, and serum BDNF levels can be used as a biomarker for drug efficacy.

Aged↗

PubMed2006

B(0) homogeneity throughout the monkey brain is strongly improved in the sphinx position as compared to the supine position.

PURPOSE: To map B(0) distortions throughout the monkey brain in the two positions commonly used for NMR studies (the prone sphinx position and the supine position) in order to test the hypothesis that B(0) homogeneity in the sphinx position is significantly improved as compared to the supine position. MATERIALS AND METHODS: Three macaque monkeys were installed in the two positions in a 3T whole-body MR system without shim correction. B(0) maps were acquired using a 3D gradient double-echo sequence, and field dispersion throughout the brain was quantified. In addition, field maps and localized (1)H spectra were acquired after first-order shimming was performed. RESULTS: The field maps collected in the three animals were highly reproducible. B(0) dispersion throughout the brain was typically two to three times greater in the supine position than in the sphinx position. Although first-order shimming proved relatively more efficient in the supine position, B(0) dispersion still remained greater in the supine than in the sphinx position. These findings can be explained by the thickness of outer brain tissues. CONCLUSION: This work demonstrates that the sphinx position is highly favorable in terms of B(0) homogeneity. It should prove useful for NMR exploration of the monkey brain, particularly at high fields where B(0) inhomogeneity associated with susceptibility artifacts is increased.

Animals↗

PubMed2005

Optimized diffusion-weighted spectroscopy for measuring brain glutamate apparent diffusion coefficient on a whole-body MR system.

A diffusion-weighted stimulated echo acquisition mode sequence was implemented in order to measure the glutamate apparent diffusion coefficient (ADC) in the monkey brain on a whole-body 3 T system. TE and TM were adjusted for maximizing glutamate signal intensity. Glutamate ADC was measured in a 5.8 mL voxel made of gray and white matter in macaque monkeys. The effect of post-processing on the estimated ADC was carefully assessed and appeared to be critical. Individual scan phasing and macromolecule subtraction corrected for approximately 25% and approximately 15% biases in glutamate ADC, respectively. Proper data processing yielded ADC values of 0.21 +/- 0.03 microm(2)/ms for glutamate, 0.15 +/- 0.04 microm(2)/ms for N-acetylaspartate + N-acetylaspartylglutamate, 0.12 +/- 0.03 microm(2)/ms for creatine, 0.11 +/- 0.05 microm(2)/ms for choline and 0.18 +/- 0.04 microm(2)/ms for myo-inositol.

Animals↗