TY - JOUR
T1 - Methamphetamine causes persistent immune dysregulation
T2 - A cross-species, translational report
AU - Loftis, Jennifer M.
AU - Choi, Dongseok
AU - Hoffman, William
AU - Huckans, Marilyn S.
N1 - Funding Information:
Acknowledgments This material is based upon research in part supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research, and Development and Clinical Sciences Research and Development. Additional funding for this study was provided by the National Institute on Drug Abuse (P50 DA18165). The authors would like to thank the Methamphetamine Abuse Research Center at Oregon Health & Science University, and the Portland VAMC for providing research and administrative support.
PY - 2011/7
Y1 - 2011/7
N2 - 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.
AB - 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.
KW - Adhesion molecules
KW - Chemokines
KW - Cytokines
KW - Methamphetamine
KW - Neuroinflammation
KW - Substance abuse
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U2 - 10.1007/s12640-010-9223-x
DO - 10.1007/s12640-010-9223-x
M3 - Article
C2 - 20953917
AN - SCOPUS:79958133175
SN - 1029-8428
VL - 20
SP - 59
EP - 68
JO - Neurotoxicity Research
JF - Neurotoxicity Research
IS - 1
ER -