Postmortem brains of subjects diagnosed with human immunodeficiency virus-1 (HIV
) associated neurocognitive disorders (HAND
) exhibit loss of dendrites
. However, the mechanisms by which synapses are damaged are not fully understood.
Dendrite length and remodeling occurs via microtubules (MTs) the dynamics of which are regulated by microtubule binding proteins, including MT associated protein 2 (MAP2). The HIV
is neurotoxic and interferes with neuronal MTs. We measured MAP2 concentrations in human cerebrospinal fluid (CSF) and MAP2 immunoreactivity in rat cortical neurons exposed to HIV
First, we examined whether HIV
affects MAP2 levels by analyzing the CSF of 27 persons living with HIV
(PLH) whose neurocognitive performance had been characterized. We then used rat cortical neurons to study the mechanisms of HIV
-mediated dendritic loss.
PLH who had HAND
had greater MAP2 concentrations within the CSF than cognitive normal PLH. In cortical neurons, the deleterious effect of HIV
on MAP2 positive dendrites
occurred through a gp120
-mediated mechanism. The neurotoxic effect of HIV
was blocked by a CCR5 antagonist and prevented by Helix-A, a peptide that displaces gp120
from binding to MTs, conjugated to a nanolipoprotein particle delivery platform.
Our findings support that HIV
at least partially effects its neurotoxicity via neuronal cytoskeleton modifications and provide evidence of a new therapeutic compound that could be used to prevent the HIV