Muhammed Bishir, Wenfei Huang, Ilker K Sariyer, Sulie L Chang
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引用次数: 0
Abstract
Misuse of opioids is a major comorbidity in people with HIV (PWH). Neurological abnormalities and opioid addiction seen in PWH involve the interplay among signaling pathways. However, the impact of HIV proteins on morphine dependence is understudied. We aimed to understand the modulation of the opioid dependence genes and signaling pathways in the striatum (Str) and prefrontal cortex (PFC) of PWH. HIV-1 transgenic (HIV-1Tg) rats and F344 control animals were given 2 and 4 pellets of morphine (75-mg/pellet)/placebo on Days 1 and 2, respectively, via subcutaneous implantation. On Day 5, at morphine tolerance the rats were sacrificed, Str and PFC were collected for RNA isolation and cDNA preparation. A PCR-array was used to examine the expression of the 65 opioid dependance genes. Varying numbers of genes were significantly upregulated in the Str and PFC of morphine treated rats. Fold change values were uploaded to QIAGEN Ingenuity Pathway Analysis, to study the signaling pathways associated with the treatment conditions. CREB signaling in neurons and Neuroinflammation signaling pathway were highly activated in the Str of both male and female HIV-1Tg rats given morphine. Gαq signaling and S100 family signaling were activated in female HIV-1Tg rats received morphine. Similarly, in the PFC, synthesis of IP3, CREB Signaling in neurons, Gαq signaling in males and CREB Signaling in neuron, and Gαq signaling in females were activated. Using bioinformatic analysis, we identified key signaling pathways and gender dependent changes in the opioid dependent gene expression and pathway enrichment of HIV-1Tg rats at morphine tolerance.
期刊介绍:
The Journal of NeuroVirology (JNV) provides a unique platform for the publication of high-quality basic science and clinical studies on the molecular biology and pathogenesis of viral infections of the nervous system, and for reporting on the development of novel therapeutic strategies using neurotropic viral vectors. The Journal also emphasizes publication of non-viral infections that affect the central nervous system. The Journal publishes original research articles, reviews, case reports, coverage of various scientific meetings, along with supplements and special issues on selected subjects.
The Journal is currently accepting submissions of original work from the following basic and clinical research areas: Aging & Neurodegeneration, Apoptosis, CNS Signal Transduction, Emerging CNS Infections, Molecular Virology, Neural-Immune Interaction, Novel Diagnostics, Novel Therapeutics, Stem Cell Biology, Transmissable Encephalopathies/Prion, Vaccine Development, Viral Genomics, Viral Neurooncology, Viral Neurochemistry, Viral Neuroimmunology, Viral Neuropharmacology.