Journal article
Nef expression in astrocytes of the nucleus accumbens disrupts the glutamate cycle and increases cocaine seeking behavior in rats
Journal of neurovirology, v 29(Suppl 1), pp S26-S26
18 Sep 2023
Abstract
Cocaine use prevalence is higher in HIV-infected individuals and can contribute to the vulnerability to and development of HIV associated neurocognitive disorders (HAND). Cocaine and HIV contribute to neuronal damage during progression of HAND through dysregulation of glutamate homeostasis, including reduction of glutamate transporter (GLT-1) and cystine/glutamate antiporter (xCT) on astrocytes. Infected astrocytes also serve as a viral reservoir and produce HIV neurotoxic proteins, with Nef being the most abundant. In this study, we focus on the possible intersection of HIV-1 Nef neurotoxicity and cocaine consumption by examining the role of astrocytic Nef expression on the glutamate cycle. We hypothesized that combined cocaine exposure and astrocytic Nef expression would exacerbate glutamate excitation inducing neurophysiological changes that strengthen synaptic transmission and reinforce cocaine-seeking behavior. To test this, we infused a lentiviral vector expressing Nef, or an empty vector, into the brains of Sprague Dawley male and female rats. After five weeks, we injected the rats intraperitoneally with one dose of cocaine or saline and collected brain tissues 24 h later for molecular analysis. Western blot and immunofluorescence (IF) analysis of GLT-1 and xCT showed a significant decrease in glutamate transporter expression in Nef, cocaine, and Nef+ cocaine groups compared to the control. IF analysis also showed high GFAP expression (astrogliosis) in the Nef group. Behavioral data, using a cocaine self-administration paradigm, also showed that rats with Nef expression have an increased cocaine-induced seeking behavior compared to control group. In conclusion, our results suggest a convergence of HIV-1 Nef and cocaine in glutamate dysregulation and neurotoxicity that may explain the increase in cocaine seeking.
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Details
- Title
- Nef expression in astrocytes of the nucleus accumbens disrupts the glutamate cycle and increases cocaine seeking behavior in rats
- Creators
- Jessalyn Gabrielle Pla Tenorio - Ponce Health Sciences UniversityBethzaly Velazquez-Perez - Ponce Health Sciences UniversityMyrella Cruz-Rentas - Ponce Health Sciences UniversityAna Vargas-Virella - Ponce Health Sciences UniversityMaria Colon-Romero - Ponce Health Sciences UniversityMarian T. Sepulveda-Orengo - Ponce Health Sciences UniversityRichard J Noel - Ponce Health Sciences University
- Publication Details
- Journal of neurovirology, v 29(Suppl 1), pp S26-S26
- Conference
- 19th International Symposium on NeuroVirology, 19th (Montreal, Quebec, Canada, 02 Oct 2023–05 Oct 2023)
- Publisher
- SPRINGER
- Number of pages
- 1
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:001091156000001
- Scopus ID
- 2-s2.0-85171807166
- Other Identifier
- 991021961315604721
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Neurosciences
- Virology