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Combining Laser Capture Microdissection and Microfluidic qPCR to Analyze Transcriptional Profiles of Single Cells: A Systems Biology Approach to Opioid Dependence
09:54

Combining Laser Capture Microdissection and Microfluidic qPCR to Analyze Transcriptional Profiles of Single Cells: A Systems Biology Approach to Opioid Dependence

Published on: March 8, 2020

Differential expression and HIV-1 regulation of μ-opioid receptor splice variants across human central nervous system

Seth M Dever1, Ruqiang Xu, Sylvia Fitting

  • 1Department of Pharmacology & Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298-0613, USA. smdever@vcu.edu

Journal of Neurovirology
|April 25, 2012
PubMed

Insights

Micro-opioid receptor (MOR) splice variants show cell-specific expression in the central nervous system (CNS). HIV-1 differentially regulates MOR variants, impacting signaling and potentially neurocognitive impairment in infected individuals.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Immunology

Background:

  • The micro-opioid receptor (MOR) exhibits extensive alternative splicing, leading to numerous splice variants.
  • The functional significance of MOR variants, beyond MOR-1, in human immunodeficiency virus type-1 (HIV-1) pathogenesis within the central nervous system (CNS) remains largely unexplored.

Purpose of the Study:

  • To investigate the differential expression of MOR variants across CNS cell types.
  • To determine how HIV-1 infection influences MOR variant expression profiles.
  • To explore the functional consequences of MOR variant expression on intracellular signaling pathways.

Main Methods:

  • Quantitative analysis of MOR variant mRNA expression in astroglia, microglia, and neurons.
  • Experimental expression of MOR variants and G protein qi5 in HEK-293T cells.
  • Assessment of calcium/NFAT signaling in response to morphine treatment.

Main Results:

  • MOR-1A mRNA was detected in astroglia, microglia, and neurons, while MOR-1 and MOR-1X were exclusively found in astroglia.
  • Expression of different MOR variants in HEK-293T cells led to varied calcium/NFAT signaling responses to morphine.
  • MOR variant expression patterns were differentially regulated by HIV-1 and may be altered in the brains of HIV-infected individuals with neurocognitive impairment.

Conclusions:

  • MOR-1 may not be the predominant MOR splice variant in all CNS cell types.
  • Distinct MOR splice variants possess potentially differing functions in CNS processes.
  • HIV-1 infection can alter MOR variant expression, suggesting a role in CNS pathogenesis and neurocognitive outcomes.

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