Related Experiment Video
Updated: Jan 23, 2026
10:12
Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity
Published on: June 14, 2024
2.6K
Nitrosative Stress Is Associated with Dopaminergic Dysfunction in the HIV-1 Transgenic Rat
Swati Shah1, Dragan Maric2, Frank Denaro3
1Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, NIH, Bethesda, Maryland.
The American Journal of Pathology
|June 25, 2019
Summary
HIV-associated neurocognitive disorders involve oxidative stress, with increased nitrosative stress markers and no antioxidant system adaptation in aging HIV-1 transgenic rats. This suggests dopaminergic neuron damage contributes to cognitive decline.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Antiretroviral therapy has reduced HIV mortality, but HIV-associated neurocognitive disorders (HAND) remain prevalent.
- The precise neuropathology of HAND is not fully understood, with oxidative stress proposed as a key mechanism.
Purpose of the Study:
- To investigate the role of oxidative and nitrosative stress in the neuropathology of HAND using an HIV-1 transgenic rat model.
- To examine the expression of key oxidative stress markers and antioxidant systems in different age groups of HIV-1 Tg rats.
Main Methods:
- Utilized HIV-1 transgenic (Tg) rats across different age groups (1-month, 7-9 months, 18-20 months) and age-matched controls.
- Assessed striatal expression of NADPH oxidase-4, neuronal nitric oxide synthase, and 3-nitrotyrosine (3-NT) via immunostaining.
- Evaluated the expression of antioxidant system components, including nuclear factor-erythroid 2-related factor 2 (Nrf2) and its downstream targets.
Main Results:
- Increased striatal NADPH oxidase-4 and neuronal nitric oxide synthase expression were observed in adult (7-9 months) and old (18-20 months) Tg rats compared to controls.
- 3-nitrotyrosine (3-NT) immunostaining significantly increased with age in Tg rats, indicating nitrosative stress.
- No concurrent induction of antioxidant systems (Nrf2, thioredoxin, glutathione) was detected, suggesting a lack of adaptive response.
- 3-NT colocalized with neurofilament proteins, and decreased tyrosine hydroxylase and dopamine transporter expression were noted in old Tg rats, pointing to dopaminergic dysfunction.
Conclusions:
- The HIV-1 Tg rat brain exhibits nitrosative stress without compensatory antioxidant adaptation.
- Modification of striatal neurofilament proteins by 3-NT is implicated in dopaminergic neuronal loss and dysfunction in aging HIV-1 Tg rats.
- These findings highlight nitrosative stress as a critical factor in the development of HAND.
Related Concept Videos
01:19Nitrosation of Enols
9.3K
The nitrosation reaction is one of the methods of preparing 1,2-diketones. The enol tautomer of the starting ketone reacts with sodium nitrite in hydrochloric acid, generating the 1,2-diketone after hydrolysis.
9.3K
00:53Transgenic Organisms
33.2K
Overview
33.2K
02:50Transgenic Plants
8.5K
Recombinant DNA technology called transgenesis is often used to add a foreign gene or remove a detrimental gene from an organism. Such genetically modified organisms are called transgenic organisms.
The first-ever transgenic plant was a tobacco plant developed in 1983 that showed resistance against the tobacco mosaic virus. Since then, many transgenic plants have been developed and commercialized for improving the agricultural, ornamental, and horticultural value of a crop plant. Transgenic...
The first-ever transgenic plant was a tobacco plant developed in 1983 that showed resistance against the tobacco mosaic virus. Since then, many transgenic plants have been developed and commercialized for improving the agricultural, ornamental, and horticultural value of a crop plant. Transgenic...
8.5K
02:02Responses to Salt Stress
14.5K
Salt stress—which can be triggered by high salt concentrations in a plant’s environment—can significantly affect plant growth and crop production by influencing photosynthesis and the absorption of water and nutrients.
14.5K
02:45Responses to Heat and Cold Stress
14.7K
Every organism has an optimum temperature range within which healthy growth and physiological functioning can occur. At the ends of this range, there will be a minimum and maximum temperature that interrupt biological processes.
14.7K
01:21General State of Stress
629
The general state of stress within a material can be accurately depicted using a stress tensor. This tensor encapsulates the internal forces distributed within a material subjected to external forces or deformations.
Specifically, consider a tetrahedral element where one face, labeled XYZ, is perpendicular to the line OA, and the remaining faces align with the coordinate axes with point O as the origin. At any point, such as point O, the stress tensor can be used to determine the stress...
Specifically, consider a tetrahedral element where one face, labeled XYZ, is perpendicular to the line OA, and the remaining faces align with the coordinate axes with point O as the origin. At any point, such as point O, the stress tensor can be used to determine the stress...
629