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Age-Related Decrease in Tyrosine Hydroxylase Immunoreactivity in the Substantia Nigra and Region-Specific Changes in
David R Goulding1, Andrew Kraft2,3, Peter R Mouton4
1Comparative Medicine Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
Neurotoxicity Research
|July 10, 2019
Summary
This study in HIV-1 Tg rats reveals age-related behavioral and dopaminergic changes, with early microglia activation in the striatum but limited neuroinflammation, offering insights into HIV-1-associated neurocognitive disorders (HAND).
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Animal models are crucial for understanding human immunodeficiency virus-1 (HIV-1)-associated neurocognitive disorders (HAND).
- HIV-1 transgenic (Tg) rats mimic neuropathological features seen in patients on combined antiretroviral therapy (cART).
- Previous studies show conflicting data on neuroinflammation and glial reactivity in these rats.
Purpose of the Study:
- To investigate age-related behavioral differences, dopaminergic function, neuroinflammation, and glial reactivity in HIV-1 Tg male rats.
- To clarify the role of HIV proteins in neurocognitive deficits and brain changes.
- To assess alterations in specific brain regions like the striatum, hippocampus, cortex, and substantia nigra.
Main Methods:
- Behavioral tests including rotarod performance and active avoidance latency were conducted at 6 and 12 weeks of age.
- Tyrosine hydroxylase (TH) immunoreactivity was assessed in the substantia nigra (SN) at various ages (2-8 months).
- Astrocyte and microglia morphology, and mRNA levels of key inflammatory markers (Iba1, Cd11b, Il1α, Cxcr3, Icam, Tnfa) were analyzed in different brain regions at 5 months.
Main Results:
- HIV-1 Tg rats exhibited diminished rotarod performance and memory deficits.
- A decrease in TH+ immunoreactivity was observed in the SN at 8 months, but not earlier.
- Microglia in the striatum showed subtle morphological changes and altered mRNA expression, with some inflammatory markers decreasing, while the hippocampus showed slight elevations in Tnfa and Cd11b mRNA.
Conclusions:
- HIV proteins induce age-related effects on the nigrostriatal dopaminergic system.
- Early microglial responses occur in the striatal synaptic regions.
- Significant neuroinflammation across brain regions was not evident, suggesting a complex interplay between viral proteins, glial cells, and neuronal function in HAND pathogenesis.
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