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HIV-1 Subtypes B and C Tat Differentially Impact Synaptic Plasticity Expression and Implicates HIV-Associated Neurocognitive Disorders§

[ Vol. 12 , Issue. 6 ]

Author(s):

Thangavel Samikkannu, Venkata S.R. Atluri, Adriana Y. Arias, Kesava V.K. Rao, Carmen T. Mulet, Rahul D. Jayant and Madhavan P.N. Nair   Pages 397 - 405 ( 9 )

Abstract:


Earlier studies have established that infection with HIV-1 subtypes (clades) might differentially influence the neuropathogenesis of HIV-1-associated neurocognitive dysfunction (HAND). HIV-1 Trans activator of transcription protein (Tat) is of considerable significance and plays a major role in the central nervous system (CNS) dysfunction. However, these HIV-1 clades exert diverse cellular effects that leads to neuropathogenic dysfunction has not been well established. We hypothesized that the HIV-1 clade B and clade C Tat proteins effect synaptic plasticity expression in neuroblastoma cells (SK-N-MC) by diverse methods, and accordingly modulates the development of HAND. In the present study, we have analyzed important and highly expressed 84 key human synaptic plasticity genes expression which differentially impact in clade B and clade C Tat treated SK-N-MC cells using RT2 Profile PCR Array human Synaptic Plasticity kit. Observed results demonstrate that out of 84 key synaptic plasticity genes, 36 and 25 synaptic genes were substantially (≥3 fold) up-regulated and 5 and 5 genes considerably (≥3 fold) down-regulated in clade B and clade C Tat treated cells, respectively, compared to the control SK-N-MC. We have also estimated the levels of glutamine and glutamate in HIV-1 clade B and C Tat exposed SK-N-MC cells compared to untreated cells. Our results indicate that levels of glutamate, glutamine and expression of synaptic plasticity genes were highly dysregulated by HIV-1 clade B Tat compared to clade C Tat in SK-N-MC cells. In summary, this study suggests that clade B Tat substantially potentiates neuronal toxicity and further dysregulated synaptic plasticity genes in SK-N-MC may contribute to the severe neuropathogenesis linked with HAND.

Keywords:

HIV-subtypes, SK-N-MC, synaptic plasticity, Tat.

Affiliation:

Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, ACH-1# 417B, Florida International University, Modesto A. Maidique Campus (MMC), 11200 S.W. 8th Street, Miami, FL-33199, USA.

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