Journal Article

Human Synaptic Plasticity Gene Expression Profile and Dendritic Spine Density Changes in HIV-Infected Human CNS Cells: Role in HIV-Associated Neurocognitive Disorders (HAND)

Yndart, Adriana, Reddy, Pichili V. B., Nair, Madhavan P. N., Atluri, Venkata Subba Rao, Kanthikeel, Sudheesh P.

2013

Overview

HIV-associated neurocognitive disorders (HAND) is characterized by development of cognitive, behavioral and motor abnormalities, and occur in approximately 50% of HIV infected individuals. Our current understanding of HAND emanates mainly from HIV-1 subtype B (clade B), which is prevalent in USA and Western countries. However very little information is available on neuropathogenesis of HIV-1 subtype C (clade C) that exists in Sub-Saharan Africa and Asia. Therefore, studies to identify specific neuropathogenic mechanisms associated with HAND are worth pursuing to dissect the mechanisms underlying this modulation and to prevent HAND particularly in clade B infection. In this study, we have investigated 84 key human synaptic plasticity genes differential expression profile in clade B and clade C infected primary human astrocytes by using RT(2) Profile PCR Array human Synaptic Plasticity kit. Among these, 31 and 21 synaptic genes were significantly (≥3 fold) down-regulated and 5 genes were significantly (≥3 fold) up-regulated in clade B and clade C infected cells, respectively compared to the uninfected control astrocytes. In flow-cytometry analysis, down-regulation of postsynaptic density and dendrite spine morphology regulatory proteins (ARC, NMDAR1 and GRM1) was confirmed in both clade B and C infected primary human astrocytes and SK-N-MC neuroblastoma cells. Further, spine density and dendrite morphology changes by confocal microscopic analysis indicates significantly decreased spine density, loss of spines and decreased dendrite diameter, total dendrite and spine area in clade B infected SK-N-MC neuroblastoma cells compared to uninfected and clade C infected cells. We have also observed that, in clade B infected astrocytes, induction of apoptosis was significantly higher than in the clade C infected astrocytes. In conclusion, this study suggests that down-regulation of synaptic plasticity genes, decreased dendritic spine density and induction of apoptosis in astrocytes may contribute to the severe neuropathogenesis in clade B infection.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Abnormalities / Acquired immune deficiency syndrome / AIDS / AIDS Dementia Complex - genetics / AIDS Dementia Complex - physiopathology / AIDS Dementia Complex - virology / Analysis / Apoptosis / Astrocytes / Astrocytes - metabolism / Astrocytes - pathology / Astrocytes - virology / Behavioral plasticity / Biology / Brain / Carbocyanines - metabolism / Cells, Cultured / Central nervous system / Central Nervous System - metabolism / Central Nervous System - pathology / Central Nervous System - virology / Cognition / Cognitive ability / Confocal / Cytometry / Dementia / Dendrites / Dendritic plasticity / Dendritic spines / Dendritic Spines - metabolism / Dendritic Spines - pathology / Dendritic Spines - virology / Dendritic structure / Density / Disorders / Down-Regulation - genetics / Flow Cytometry / Gene expression / Gene regulation / Genes / Glutamate receptors / Glutamic acid receptors / Health aspects / HIV / HIV infections / HIV patients / HIV-1 - physiology / Human immunodeficiency virus / Humans / Immunology / Infection / Infections / Lymphocytes B / Medical research / Medicine / Membrane Proteins - metabolism / Memory / Microscopic analysis / Microscopy, Confocal / Morphology / N-Methyl-D-aspartic acid receptors / Neuroblastoma / Neuroblastoma cells / Neuroblasts / Neuronal Plasticity - genetics / Neuropathogenesis / Neuropathology / Neurotoxicity / Pharmacology / Plasticity / Plasticity (behavioral) / Plasticity (dendritic) / Plasticity (synaptic) / Postsynaptic density / Proteins / Regulatory proteins / Spine / Studies / Synapses - genetics / Synaptic plasticity / Transcriptome