Modulation of simian immunodeficiency virus neuropathology by dopaminergic drugs.
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-alpha 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.
Czub
S
S
Pathological Institute, University Würzburg, Wuerzburg, Germany.
Czub
M
M
Koutsilieri
E
E
Sopper
S
S
Villinger
F
F
Müller
J G
JG
Stahl-Hennig
C
C
Riederer
P
P
Ter Meulen
V
V
Gosztonyi
G
G
D000818:Animals; D002452:Cell Count / Q000379:methods; D020805:Central Nervous System Viral Diseases / Q000473:pathology / Q000821:virology; D015259:Dopamine Agents / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007249:Inflammation / Q000209:etiology / Q000473:pathology / Q000821:virology; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007980:Levodopa / Q000009:adverse effects; D008253:Macaca mulatta; D008995:Monoamine Oxidase / Q000378:metabolism; D012642:Selegiline / Q000009:adverse effects; D016097:Simian Acquired Immunodeficiency Syndrome / Q000473:pathology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000502:physiology; D013194:Staining and Labeling / Q000379:methods; D018709:Statistics, Nonparametric; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D015259:Dopamine Agents; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D012642:Selegiline; D007980:Levodopa; D008995:Monoamine Oxidase