Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Novel RNA-Seq Signatures Post-Methamphetamine and Oxycodone Use in a Model of HIV-Associated Neurocognitive Disorders

Pranavi Athota
ORCID logo ,
Nghi M Nguyen
ORCID logo ,
Victoria L Schaal
ORCID logo ,
Sankarasubramanian Jagadesan
ORCID logo ,
Chittibabu Guda
ORCID logo ,
Sowmya V Yelamanchili
ORCID logo ,
Gurudutt Pendyala
* ORCID logo
Version 1 : Received: 8 July 2023 / Approved: 10 July 2023 / Online: 10 July 2023 (11:34:14 CEST)

A peer-reviewed article of this Preprint also exists.

Athota, P.; Nguyen, N.M.; Schaal, V.L.; Jagadesan, S.; Guda, C.; Yelamanchili, S.V.; Pendyala, G. Novel RNA-Seq Signatures Post-Methamphetamine and Oxycodone Use in a Model of HIV-Associated Neurocognitive Disorders. Viruses 2023, 15, 1948. Athota, P.; Nguyen, N.M.; Schaal, V.L.; Jagadesan, S.; Guda, C.; Yelamanchili, S.V.; Pendyala, G. Novel RNA-Seq Signatures Post-Methamphetamine and Oxycodone Use in a Model of HIV-Associated Neurocognitive Disorders. Viruses 2023, 15, 1948.

Abstract

In the 21st century, the effects of HIV-associated neurocognitive disorders (HAND) have been significantly reduced in individuals due to the development of antiretroviral therapies (ARTs). However, the growing epidemic of polysubstance use (PSU) has led to concern for the effects of PSU on HIV-seropositive individuals. To effectively treat individuals affected by HAND, it is critical to understand the biological mechanisms affected by PSU including identification of novel markers. To fill this important knowledge gap, we used an in vivo HIV-Transgenic (HIV-Tg) animal model, to investigate the effects of the combined use of chronic methamphetamine (METH) and oxycodone (oxy). RNA-Seq analysis on the striatum - a brain region that is primarily targeted by both HIV and drugs of abuse - identified key differentially expressed markers post-METH and oxy exposure. Furthermore, ClueGO analysis and Ingenuity Pathway Analysis (IPA) revealed crucial molecular and biological functions associated with ATP-activated adenosine receptor, neuropeptide hormone activity, and the oxytocin signaling pathway to be altered between the different treatment groups. The current study further reveals the harmful effects of chronic PSU and HIV infection that can subsequently impact neurological outcomes in polysubstance users with HAND.

Keywords

Polysubstance use; methamphetamine; oxycodone; HIV; transgenic rat; RNA-sequencing, bioinformatics

Subject

Medicine and Pharmacology, Neuroscience and Neurology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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