title: Morphine causes persistent induction of nitrated neurofilaments in cortex and subcortex even during abstinence.
abstract: Morphine has a profound role in neurofilament (NF) expression. However, there are very few studies on the fate of NFs during morphine abstinence coinciding with periods of relapse. Mice were treated chronically with morphine to render them tolerant to and dependent on morphine and sacrificed thereafter while another group, treated similarly, was left for 2 months without morphine. A long-lasting alteration in the stoichiometric ratio of the three NFs was observed under both conditions in both the cortex and subcortex. Morphine abstinence caused significant alterations in the phosphorylated and nitrated forms of the three NF subunits. Nitrated neurofilament light polypeptide chain (NFL) was significantly increased during chronic morphine treatment which persisted even after 2 months of morphine withdrawal. Mass spectrometric analysis following two-dimensional gel electrophoresis (2DE)-gel electrophoresis of cytoskeleton fractions of both cortex and subcortex regions identified enzymes associated with energy metabolism, cytoskeleton-associated proteins as well as NFs which showed sustained regulation even after abstinence of morphine for 2 months. It is suggestive that alteration in the levels of some of these proteins may be instrumental in the increased nitration of NFL during morphine exposure. Such gross alteration in NF dynamics is indicative of a concerted biological process of neuroadaptation during morphine abstinence.
authors: Neurobiology Department, Cell Biology & Physiology Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India.
authors: A
authors: A
authors: Pal
authors: Neurobiology Department, Cell Biology & Physiology Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India. Electronic address: sdas@iicb.res.in.
authors: S
authors: S
authors: Das
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D007031:Hypothalamus / Q000378:metabolism; D007382:Intermediate Filaments / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008636:Mesencephalon / Q000378:metabolism; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000378:metabolism*; D009294:Narcotics / Q000494:pharmacology*; D009574:Nitro Compounds / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D040901:Proteomics; D020665:Septum of Brain / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism
chemical_list: D009294:Narcotics; D009574:Nitro Compounds; D009020:Morphine
keywords: cytoskeleton; morphine; neurofilaments; nitration; proteomics; withdrawal