Biomedical subjects

Jean-Lud Cadet

Publications and source records attributed to Jean-Lud Cadet.

4 recordsLinked to original sources

PubMed2006

An in vitro model of human dopaminergic neurons derived from embryonic stem cells: MPP+ toxicity and GDNF neuroprotection.

Human embryonic stem cells (hESCs) can proliferate indefinitely yet also differentiate in vitro, allowing normal human neurons to be generated in unlimited numbers. Here, we describe the development of an in vitro neurotoxicity assay using human dopaminergic neurons derived from hESCs. We showed that the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)), which produces features of Parkinson's disease in humans, was toxic for hESC-derived dopaminergic neurons. Treatment with glial cell line-derived neurotrophic factor protected tyrosine hydroxylase-positive neurons against MPP(+)-induced apoptotic cell death and loss of neuronal processes as well as against the formation of intracellular reactive oxygen species. The availability of human dopaminergic neurons, derived from hESCs, therefore allows for the possibility of directly examining the unique features of human dopaminergic neurons with respect to their responses to pharmacological agents as well as environmental and chemical toxins.

1-Methyl-4-phenylpyridinium↗

PubMed2005

Altered brain tissue composition in heavy marijuana users.

Marijuana is the most widely used illicit substance in the United States; however, previous imaging studies have not detected altered brain structure in marijuana users compared to non-users. Voxel-based morphometry was used to investigate possible differences in brain tissue composition in a group of 11 heavy marijuana users and a group of 8 non-users. All participants were male. Statistical comparisons were made at the voxel level on T1-weighted magnetic resonance images to determine differences in gray matter and white matter tissue density. Compared to non-users, marijuana users had lower gray matter density in a cluster of voxels in the right parahippocampal gyrus (P = 0.0001), and greater density bilaterally near the precentral gyrus and the right thalamus (P < 0.04). Marijuana users also had lower white matter density in the left parietal lobe (P = 0.03), and higher density around the parahippocampal and fusiform gyri on the left side compared to non-users (P < 0.002). Longer duration of marijuana use (in years) was significantly correlated with higher white matter tissue density in the left precentral gyrus (P = 0.045). Our preliminary results suggest evidence of possible structural differences in the brain of heavy marijuana users, and localize regions for further investigation of the effects of marijuana in the brain.

Adult↗

PubMed2003

Frontal cortical tissue composition in abstinent cocaine abusers: a magnetic resonance imaging study.

Cocaine abusers exhibit impairment of executive cognitive functions that are mediated by the frontal cortex. This work tested for structural (i.e., tissue composition) abnormalities that may underlie such performance deficits. Research participants were cocaine abusers (n = 14) abstinent for 20 days and a non-drug-using comparison group (n = 11), who underwent magnetic resonance imaging (T1-weighted scans of the brain). Gray matter and white matter tissue densities were determined using voxel-based morphometry with small volume correction based on a priori hypotheses derived from functional imaging of the same subjects. Cocaine abusers had significantly lower gray matter tissue density than did the non drug users in 10 of 13 small volumes analyzed in the frontal cortex [bilateral anterior cingulate gyrus (infragenual and perigenual regions) and medial orbitofrontal cortex and the lateral orbitofrontal cortex and middle/dorsal cingulate gyrus in the right hemisphere]. No group differences were found in white matter density of the frontal cortex. These results extend our previous findings of defective frontal cortical activation (indexed by cerebral blood flow) in cocaine abusers to include abnormalities in gray matter tissue density in the same frontal cortical regions.

Adult↗

PubMed2002

Chronic cocaine increases kappa-opioid receptor density: lack of effect by selective dopamine uptake inhibitors.

Continuous infusion of cocaine or the selective dopamine uptake inhibitors GBR 12909 or RTI-117 increases locomotor stimulation, to which partial tolerance occurs. In addition, all three drugs produce significant decreases in tyrosine hydroxylase immunoreactivity in caudate putamen and nucleus accumbens core, suggesting a decreased dopaminergic tone. An interaction between cocaine and opioids has long been documented. Chronic cocaine significantly increases mu and kappa-opioid receptors and treatment with a kappa-opioid agonist markedly reduces the behavioral effects of cocaine. In addition, chronic cocaine, but not GBR 12909, increases prodynorphin gene expression in caudate putamen. To further understand the interaction between cocaine and the kappa-opioid system, the effects of a chronic continuous infusion for 14 days of cocaine or one of the selective dopamine uptake inhibitors GBR 12909 or RTI-117 via osmotic minipump were examined on kappa-opioid receptors using the selective kappa-opioid ligand [3H] U-69593. [3H] U-69593 binding density was significantly increased in caudate putamen, nucleus accumbens shell, claustrum, and endopiriform nucleus after cocaine, while neither GBR 12909 nor RTI-117 had any effect. The increased kappa-opioid receptor densities observed following cocaine are likely not related to dopamine uptake inhibition, since they were not produced by selective dopamine uptake inhibitors. These findings suggest that regulation of kappa-opioid receptors by cocaine may be via inhibition of serotonin or norepinephrine uptake, by a combination of effects on two or three monoamine transporters, or by a mechanism unrelated to transporter inhibition.

Animals↗