Einfluss der SIV-Infektion und einer antiretroviralen Therapie auf die Expression von vesikulären Transmitterproteinen im Striatum von Rhesus Affen

Since the outbreak of the AIDS pandemic complex cognitive and sensorimotor complications in the course of a HIV-infection have been observed. They are summarized as HAND (HIV-associated neurocognitive diseases) and still pose, in spite of antiretroviral therapy, a relevant public health and socioeconomic problem. Prevention and treatment of HAND are not solved yet satisfactorily. Neuroinflammation in the CNS is considered to be an important pathogenetic factor in the development of HAND. Among others, regions-specific changes in cerebral transmitter systems provide another factor of HAND-associated neurological dysfunction. The striatum has been shown to be particulary vulnerable during a HIV-infection. The aim of the present thesis was to examine transient and permanent changes of classical neurotransmitter systems in the striatum in the course of SIV-infection of rhesus macaques and their antiretroviral therapy. In particular, it should be clarified to what extent the vesicular transporters of classical transmitter systems in the striatum are affected by the SIV-infection, and whether, as observed in other CNS regions, dissociated or concordant changes of corresponding transmitter-synthesizing enzymes occur. Furthermore, we investigated how changes of striatal transmitter enzymes and vesicular transporters relate to the neuroinflammatory signature of microglial and astrocytic reactions in the course of SIV-infection and their antiretroviral therapy. In order to answer these questions immunocytochemical analysis were performed on striatal tissues of four experimental groups in the SIV model of rhesus macaques: 1. Uninfected control group, 2. SIV-infected, without AIDS group (SIV/-AIDS), 3. SIV-infected, suffering from AIDS (SIV/+AIDS), 4. SIV-infected, suffering from AIDS and subsequently antiretroviral treatment (SIV/+AIDS/+ddG). The used striatal tissue samples are taken from the research collaboration