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

Authors

Venakata Subba Rao Alturi, Florida International University, Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine
Sudheesh P. Kanthikeel, Florida International University, Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of MedicineFollow
Pichili V.B. Reddy, Florida International University, Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of MedicineFollow
Adriana Yndart, Florida International University, Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of MedicineFollow
Madhavan P.N. Nair, Florida International University, Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of MedicineFollow

Date of this Version

4-19-2013

Document Type

Article

Abstract

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 RT2 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.

Comments

This article was originally published in PLoS ONE

Identifier

FIDC001511

Recommended Citation

Atluri VSR, Kanthikeel SP, Reddy PVB, Yndart A, Nair MPN (2013) Human Synaptic Plasticity Gene Expression Profile and Dendritic Spine Density Changes in HIV-Infected Human CNS Cells: Role in HIV-Associated Neurocognitive Disorders (HAND). PLoS ONE 8(4): e61399. doi:10.1371/journal.pone.0061399

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This work is licensed under a Creative Commons Attribution 4.0 License.