Longitudinal PET Imaging of the Serotonergic System in SIV Infected Non-Human Primates

Authors

• S Shah
• S Sinharay
• D Lee
• WC Reid
• P Wakim
• K Matsuda
• A Nath
• V Hirsch
• M Di Mascio
• DA Hammoud

Abstract

Background: Increased incidence of depression in HIV+ patients is associated with lower adherence to treatment and increased mortality. One possible underlying pathophysiology is serotonergic dysfunction. In this study, we used an animal model of HIV, the SIV-infected macaque, to longitudinally image serotonin transporter (SERT) expression before and after inoculation, using 11C-DASB (SERT ligand) PET imaging. Methods: Seven Rhesus macaques infected with a neurovirulent SIV strain (SIVsm804E) were imaged at baseline and multiple points post inoculation (P.I) follow-up. DASB binding potentials (BPND) were correlated with various disease parameters. Preliminary qPCR and epigenetic analysis was done to assess changes in SERT expression. Results: : Despite some animals showing early fluctuations, 86% of our animals eventually showed a net increase in midbrain/thalamus BPND over the course of their disease (mean increased binding between last time point and baseline= 30.2 % and 32.2 % respectively). Repeated-measures mixed model analysis showed infection duration to be predictive of midbrain BPND (p= 0.039). There was higher cortical SERT mRNA expression in 2 infected compared to 2 uninfected macaques (4.2 fold). Global methylation analysis indicated that SERT expression may be indirectly modulated by DEAF1 methylation. Conclusions: Longitudinal assessment of DASB binding in the SIV infected animals by PET suggests SERT upregulation in these animals. Increased DASB binding positively correlated with the duration of infection but did not correlate with VL. Upregulated SERT leading to lower synaptic levels of serotonin is a possible mechanism of depression in HIV+ patients and should be further evaluated.

Scientific Focus Area: Neuroscience

This page was last updated on Friday, March 26, 2021