Regulation of nonphosphorylated and phosphorylated forms of neurofilament proteins in the prefrontal cortex of human opioid addicts.

Détails

ID Serval
serval:BIB_A7BC26F14F98
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Regulation of nonphosphorylated and phosphorylated forms of neurofilament proteins in the prefrontal cortex of human opioid addicts.
Périodique
Journal of Neuroscience Research
Auteur(s)
Ferrer-Alcón M., García-Sevilla J.A., Jaquet P.E., La Harpe R., Riederer B.M., Walzer C., Guimón J.
ISSN
0360-4012 (Print)
ISSN-L
0360-4012
Statut éditorial
Publié
Date de publication
2000
Volume
61
Numéro
3
Pages
338-349
Langue
anglais
Résumé
The neurofilament (NF) proteins (NF-H, NF-M, and NF-L for high, medium, and low molecular weights) play a crucial role in the organization of neuronal shape and function. In a preliminary study, the abundance of total NF-L was shown to be decreased in brains of opioid addicts. Because of the potential relevance of NF abnormalities in opioid addiction, we quantitated nonphosphorylated and phosphorylated NF in postmortem brains from 12 well-defined opioid abusers who had died of an opiate overdose (heroin or methadone). Levels of NF were assessed by immunoblotting techniques using phospho-independent and phospho-dependent antibodies, and the relative (% changes in immunoreactivity) and absolute (changes in ng NF/microg total protein) amounts of NF were calculated. Decreased levels of nonphosphorylated NF-H (42-32%), NF-M (14-9%) and NF-L (30-29%) were found in the prefrontal cortex of opioid addicts compared with sex, age, and postmortem delay-matched controls. In contrast, increased levels of phosphorylated NF-H (58-41%) and NF-M (56-28%) were found in the same brains of opioid addicts. The ratio of phosphorylated to nonphosphorylated NF-H in opioid addicts (3.4) was greater than that in control subjects (1.6). In the same brains of opioid addicts, the levels of protein phosphatase of the type 2A were found unchanged, which indicated that the hyperphosphorylation of NF-H is not the result of a reduced dephosphorylation process. The immunodensities of GFAP (the specific glial cytoskeletol protein), alpha-internexin (a neuronal filament related to NF-L) and synaptophysin (a synapse-specific protein) were found unchanged, suggesting a lack of gross changes in glial reaction, other intermediate filaments of the neuronal cytoskeletol, and synaptic density in the prefrontal cortex of opioid addicts. These marked reductions in total NF proteins and the aberrant hyperphosphorylation of NF-H in brains of opioid addicts may play a significant role in the cellular mechanisms of opioid addiction.
Mots-clé
Adult, Age Factors, Carrier Proteins/metabolism, Chronic Disease, Drug Overdose/metabolism, Electrophoresis, Polyacrylamide Gel, Glial Fibrillary Acidic Protein/metabolism, Humans, Immunoblotting, Intermediate Filament Proteins, Male, Molecular Weight, Neurofilament Proteins/chemistry, Neurofilament Proteins/metabolism, Opioid-Related Disorders/metabolism, Phosphoprotein Phosphatases/metabolism, Phosphorylation, Prefrontal Cortex/metabolism, Synaptophysin/metabolism
Pubmed
Web of science
Création de la notice
24/01/2008 14:34
Dernière modification de la notice
20/08/2019 15:12
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