Document Detail


Methamphetamine causes persistent immune dysregulation: a cross-species, translational report.
MedLine Citation:
PMID:  20953917     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Methamphetamine (MA) dependence causes serious cognitive impairments that can persist during abstinence and negatively affect recovery outcomes. Evidence suggests that immune factors, such as cytokines, chemokines, and cellular adhesion molecules, contribute to MA-induced immune dysfunction, neuronal injury, and persistent cognitive impairments, yet the role of MA-induced brain inflammation remains unclear. To address this question, we used a cross-species, translational approach. Thirty-two male C57BL/6J mice were administered MA (1 mg/kg) or saline subcutaneously for seven consecutive days. Mice were euthanized at 72 h or 3 weeks after the last drug dose, and blood and brain samples were collected. In addition, 20 adults in remission from MA dependence and 20 non-dependent controls completed neuropsychological assessments and a blood draw. Multiplex assays were used to measure cytokine, chemokine, and intercellular adhesion molecule (ICAM-1) expression in mouse and human samples. A number of significant MA-induced changes in neuroimmune factors were observed. Of particular interest were the chemokine monocyte chemoattractant protein 1 (MCP-1) and the cellular adhesion molecule ICAM-1, which were similarly increased in the plasma of MA exposed mice as well as humans. In human participants, MA-induced changes in the cytokine and chemokine milieu were accompanied by increased cognitive impairments. Mice showing MA-induced changes in peripheral immune molecule expression also had significant brain-region specific changes in pro-inflammatory cytokines, chemokines, and ICAM-1. This cross-species, translational study suggests that chronic CNS immune dysregulation may in part contribute to the longlasting neuropsychiatric consequences of MA dependence.
Authors:
Jennifer M Loftis; Dongseok Choi; William Hoffman; Marilyn S Huckans
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-10-17
Journal Detail:
Title:  Neurotoxicity research     Volume:  20     ISSN:  1476-3524     ISO Abbreviation:  Neurotox Res     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-05-09     Completed Date:  2011-09-23     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  100929017     Medline TA:  Neurotox Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  59-68     Citation Subset:  IM    
Affiliation:
Research & Development Service, Portland VA Medical Center, 3710 SW U.S. Veterans Hospital Rd., R&D 16, Portland, OR 97239, USA. loftisj@ohsu.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
Amphetamine-Related Disorders / blood,  complications,  metabolism*
Animals
Brain / metabolism
Chemokine CCL2 / blood,  metabolism
Chemokines / blood,  metabolism
Cognition Disorders / chemically induced,  complications,  metabolism*
Cytokines / blood,  metabolism
Disease Models, Animal
Female
Humans
Immune System Diseases / chemically induced,  complications,  metabolism*
Immunologic Factors / blood,  metabolism*
Intercellular Adhesion Molecule-1 / blood,  metabolism
Male
Methamphetamine / adverse effects*
Mice
Mice, Inbred C57BL
Neuropsychological Tests
Random Allocation
Grant Support
ID/Acronym/Agency:
P50 DA18165/DA/NIDA NIH HHS; RC1 DA028537-01/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Chemokine CCL2; 0/Chemokines; 0/Cytokines; 0/Immunologic Factors; 126547-89-5/Intercellular Adhesion Molecule-1; 537-46-2/Methamphetamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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