Abstract
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Objectives Depression remains a major problem in chronically infected HIV positive patients despite the use of antiretroviral therapy (ART). A dysfunctional serotonergic system has been implicated in the pathogenesis of HIV associated depression. We therefore sought out to measure the dynamic changes in serotonin transporters (SERT) using 11C-DASB in a macaque model of SIV, before and after treatment.
Methods Two female SIV macaque were imaged with 11C-DASB at baseline (4.75 kg; 5.1 ± 0.2 mCi), after SIV infection (5.85 kg; 5.1 ± 0.1 mCi) and after treatment (4.22 kg; 5.2 ± 0.2 mCi). The PET data were acquired dynamically over 120 min using the HRRT. Various brain regions of interest (ROI) were evaluated for differences in SERT binding potential (BPND) using standard SRTM with the cerebellar cortex as reference.
Results We found reduced 11C-DASB BPND values after inoculation in the insula (-27%), amygdala (-24%), thalamus (-11%), and midbrain (-13 %), compared to pre-inoculation levels. After treatment was initiated, BPND values increased with many regions showing even higher than baseline BPND values.
Conclusions Decreased 11C-DASB BPND was seen during the acute phase of SIV infection indicating neuronal injury. This however reversed after treatment with some regions showing higher than baseline values. Our findings suggest serotonergic injury associated with the acute infection which reversed after initiation of treatment. A higher than baseline SERT expression after treatment probably reflects the additive effects of compensatory increased SERT in the residual neurons in the acute infectious phase along with recovery of the injured neurons.