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Modulation of simian immunodeficiency virus neuropathology by dopaminergic drugs

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Abstract

Drug abuse and human immunodeficiency virus (HIV) infection seem to cause cumulative damage in the central nervous system (CNS). Elevated extracellular dopamine is thought to be a prime mediator of the reinforcing effects of addictive substances. To investigate the possible role of increased dopamine availability in the pathogenesis of HIV dementia, simian immunodeficiency virus (SIV)-infected monkeys were treated with dopaminergic drugs (selegiline or l-DOPA). Both substances increased intracerebral SIV expression, combined with aggravation of infection-related neuropathology and ultrastructural alterations of dendrites in dopaminergic areas (spongiform polioencephalopathy) in asymptomatic animals. Moreover, this treatment resulted in enhanced TNF-α expression in the brains of SIV-infected animals. These findings indicate a synergistic interaction between dopamine and SIV infection on microglia activation, leading to increased viral replication and production of neurotoxic substances. Our results suggest that increased dopamine availability through dopaminergic medication or addictive substances may potentiate HIV dementia.

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Acknowledgements

The authors would like to thank Eva Bachmann, Erwin Schmidt and Evelyn Werder for excellent technical assistance, Asta Medica (Frankfurt, Germany) for providing selegiline, and Dr. Paul Kitching (NCFAD/CFIA) for critical review of the manuscript. This work was supported by grants from the Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie (01K/97 63/8 and 01 KI 0211 HIV Network) and from the Deutsche Forschungsgemeinschaft (Cz 56/1–3).

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Authors and Affiliations

  1. Pathological Institute, University Würzburg, Würzburg, Germany

    S. Czub & J. G. Müller

  2. Institute of Virology and Immunobiology, University Würzburg, Würzburg, Germany

    M. Czub, S. Sopper & V. ter Meulen

  3. Clinical Neurochemistry, Clinic and Polyclinic of Psychiatry and Psychotherapy, University Würzburg, Füchsleinstr. 15, 97080, Würzburg, Germany

    E. Koutsilieri & P. Riederer

  4. Emory University School of Medicine, Departments of Pathology and Laboratory Medicine, Atlanta, Georgia, USA

    F. Villinger

  5. Department of Virology, German Primate Center, Göttingen, Germany

    C. Stahl-Hennig

  6. Department of Neuropathology, University Clinics Benjamin Franklin, Berlin, Germany

    G. Gosztonyi

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  1. S. Czub
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Correspondence to P. Riederer.

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Czub, S., Czub, M., Koutsilieri, E. et al. Modulation of simian immunodeficiency virus neuropathology by dopaminergic drugs. Acta Neuropathol 107, 216–226 (2004). https://doi.org/10.1007/s00401-003-0801-3

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  • DOI: https://doi.org/10.1007/s00401-003-0801-3

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