Untreated Patients Dying With AIDS Have Loss of Neocortical Neurons and Glia Cells.

Sanne Simone Kaalund,Katrine Fabricius,Annette Johansen,Bente Pakkenberg

doi:10.3389/fnins.2019.01398

Abstract

Untreated human immunodeficiency virus (HIV) depletes its host CD4 cells, ultimately leading to acquired immunodeficiency syndrome (AIDS). In brain, the HIV confines itself to astrocytes and microglia, the resident brain macrophages, but does not infect oligodendrocytes and neurons. Nonetheless, cognitive symptoms associated with HIV and AIDS are attributed to loss of axons and white matter damage. We used design-based stereology to estimate the numbers of neocortical neurons and glial cells (astrocytes, oligodendrocytes, and microglia), in a series of 12 patients dying with AIDS before the era of retroviral treatments, and in 13 age-matched control brains. Relative to the control material, there was a 19% loss of neocortical neuron (p = 0.04) and a 29% reduction of oligodendrocytes (p = 0.003) in the patients with AIDS, whereas astrocyte and microglia numbers did not differ between patients and controls. Furthermore, we saw a 17% reduction in mean hemispheric volume in the AIDS group (p = 0.0015), which was driven by neocortical and white matter loss (p < 0.05), while the archicortex, subcortical gray matter, and ventricular volumes were within normal limits. Our results confirm previous reports of neuronal loss in AIDS. The new finding of oligodendrocyte loss supports the proposal that HIV in the brain provokes demyelination and axonal dysfunction and suggests that remyelination treatment strategies may be beneficial to patients suffering from HIV-associated neurocognitive deficits.

Highlights

According to The Joint United Nations Programme on human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) (UNAIDS, 2018), 37.9 million people globally are living with HIV
Neuronal loss may be restricted to the neocortex, since neuronal numbers were preserved in hippocampus of AIDS patients (Korbo and West, 2000), despite atrophy of the neuronal soma (Sá et al, 2000)
The major findings of this study are that numbers of astrocytes and microglia were normal, but the numbers of neurons and oligodendrocytes significantly were lower in brains from patients dying with AIDS in the time before combined antiretroviral therapy (cART) treatment

Summary

Introduction

According to The Joint United Nations Programme on human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) (UNAIDS, 2018), 37.9 million people globally are living with HIV. Despite public health campaigns and effective antiviral treatments, where were 1.7 million new HIV infections recorded in 2018, and a morbidity of 7,70,000 people from AIDSrelated illnesses (UNAIDS, 2018). This reflects a halving of the incidence and morbidity since (UNAIDS, 2018), which doubtless reflects the enormous efforts expended in disease control and treatment. While atrophy is not always attested by post mortem brain weight, morphometric analyses performed on autopsy material from AIDS patients indicate a 11% reduction in neocortical volume by 11 and 55% dilation of mean ventricular volume (Oster et al, 1995). Neuronal loss may be restricted to the neocortex, since neuronal numbers were preserved in hippocampus of AIDS patients (Korbo and West, 2000), despite atrophy of the neuronal soma (Sá et al, 2000)

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