Reduced neuronal population in the dorsolateral prefrontal cortex in infant macaques infected with simian
Alexandra Haddad1, Brittany Voth1, Janiya Brooks1
1Department of Physiology and Biophysics, Howard University, Washington, DC, 20059, USA.
Insights
Pediatric HIV infection causes significant neuron loss in the developing brain, specifically the dorsolateral prefrontal cortex. This neuronal depletion, observed in a macaque model, may explain neurocognitive deficits in children with HIV.
Area of Science:
- Neuroscience
- Virology
- Pediatrics
Background:
- Pediatric HIV infection is a global health crisis, with significant mother-to-child transmission rates.
- Antiretroviral therapy (ART) improves survival but access is limited, and neurological impacts like cognitive deficits persist.
- Histological data on HIV's effect on the developing brain is scarce, hindering understanding of underlying mechanisms.
Purpose of the Study:
- To investigate the impact of early-life simian immunodeficiency virus (SIV) infection on neuronal populations in the dorsolateral prefrontal cortex (dlPFC) of infant macaques.
- To correlate neuronal loss in the dlPFC with viral load in a pediatric SIV infection model.
Main Methods:
- Retrospective analysis of 11 ART-naïve infant rhesus macaques from previous studies.
- Infants were intravenously or orally inoculated with SIVmac251 and compared to uninfected controls.
- Neuronal counts and evidence of neuronal death in the dlPFC were assessed.
Main Results:
- Both SIV-infected groups exhibited significant neuron loss in the dlPFC.
- Ongoing neuronal death was observed in infected animals.
- Neuronal loss was negatively correlated with chronic viremia levels (AUC analysis).
Conclusions:
- Early-life SIV infection leads to substantial neuron loss in the dlPFC of infant macaques.
- This dlPFC neuronal depletion may underlie the neurocognitive decline observed in pediatric HIV infection.
- The findings highlight the critical need for further research into HIV's neurological effects in children.
Abstract:
Pediatric HIV infection remains a global health crisis with an estimated 150,000 new mother-to-child (MTCT) infections each year. Antiretroviral therapy (ART) has improved childhood survival, but only an estimated 53% of children worldwide have access to treatment. Adding to the health crisis is the neurological impact of HIV on the developing brain, in particular cognitive and executive function, which persists even when ART is available. Imaging studies suggest structural, connectivity, and functional alterations in perinatally HIV-infected youth. However, the paucity of histological data limits our ability to identify specific cortical regions that may underlie the clinical manifestations. Utilizing the pediatric simian immunodeficiency virus (SIV) infection model in infant macaques, we have previously shown that early-life SIV infection depletes the neuronal population in the hippocampus. Here, we expand on these previous studies to investigate the dorsolateral prefrontal cortex (dlPFC). A total of 11 ART-naïve infant rhesus macaques (Macaca mulatta) from previous studies were retrospectively analyzed. Infant macaques were either intravenously (IV) inoculated with highly virulent SIVmac251 at ~1 week of age and monitored for 6-10 weeks or orally challenged with SIVmac251 from week 9 of age onwards with a monitoring period of 10-23 weeks post-infection (19-34 weeks of age), and SIV-uninfected controls were euthanized at 16-17 weeks of age. Both SIV-infected groups show a significant loss of neurons along with evidence of ongoing neuronal death. Oral- and IV-infected animals showed a similar neuronal loss which was negatively correlated to chronic viremia levels as assessed by an area under the curve (AUC) analysis. The loss of dlPFC neurons may contribute to the rapid neurocognitive decline associated with pediatric HIV infection.
