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Mapping Astrocytic and Neuronal μ-opioid Receptor Expression in Various Brain Regions Using MOR-mCherry Reporter
Woojin Won1, Daeun Kim1,2, Eunjin Shin1
1Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon 34126, Korea.
Abstract:
The μ-opioid receptor (MOR) is a class of opioid receptors characterized by a high affinity for β-endorphin and morphine. MOR is a G protein-coupled receptor (GPCR) that plays a role in reward and analgesic effects. While expression of MOR has been well established in neurons and microglia, astrocytic MOR expression has been less clear. Recently, we have reported that MOR is expressed in hippocampal astrocytes, and its activation has a critical role in the establishment of conditioned place preference. Despite this critical role, the expression and function of astrocytic MOR from other brain regions are still unknown. Here, we report that MOR is significantly expressed in astrocytes and GABAergic neurons from various brain regions including the hippocampus, nucleus accumbens, periaqueductal gray, amygdala, and arcuate nucleus. Using the MOR-mCherry reporter mice and Imaris analysis, we demonstrate that astrocytic MOR expression exceeded 60% in all tested regions. Also, we observed similar MOR expression of GABAergic neurons as shown in the previous distribution studies and it is noteworthy that MOR expression is particularly in parvalbumin (PV)-positive neurons. Furthermore, consistent with the normal MOR function observed in the MOR-mCherry mouse, our study also demonstrates intact MOR functionality in astrocytes through iGluSnFr-mediated glutamate imaging. Finally, we show the sex-difference in the expression pattern of MOR in PV-positive neurons, but not in the GABAergic neurons and astrocytes. Taken together, our findings highlight a substantial astrocytic MOR presence across various brain regions.
Insights
The study reveals significant μ-opioid receptor (MOR) expression in astrocytes across multiple brain regions, impacting reward and pain pathways. This finding clarifies MOR
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- The μ-opioid receptor (MOR) is a G protein-coupled receptor (GPCR) crucial for reward and analgesia.
- While neuronal and microglial MOR expression is known, astrocytic MOR presence and function remain less understood.
- Previous work identified MOR in hippocampal astrocytes, linking it to conditioned place preference.
Purpose of the Study:
- To investigate the expression and function of astrocytic MOR in various brain regions beyond the hippocampus.
- To determine the extent of MOR expression in astrocytes and GABAergic neurons.
- To explore potential sex differences in MOR expression patterns.
Main Methods:
- Utilized MOR-mCherry reporter mice for visualizing MOR expression.
- Employed Imaris software for quantitative analysis of MOR distribution.
- Assessed MOR functionality in astrocytes using iGluSnFr-mediated glutamate imaging.
Main Results:
- MOR is significantly expressed in astrocytes (>60%) and GABAergic neurons across multiple brain regions, including the hippocampus, nucleus accumbens, periaqueductal gray, amygdala, and arcuate nucleus.
- MOR expression was particularly noted in parvalbumin (PV)-positive neurons.
- Astrocytic MOR functionality was confirmed, with observed sex differences in PV-positive neuron MOR expression patterns.
Conclusions:
- Astrocytes express substantial levels of MOR across diverse brain regions, suggesting a broader role in opioid signaling.
- MOR in astrocytes and specific neuronal subtypes (PV-positive) may be key targets for modulating pain and reward.
- Further research is warranted to elucidate the functional implications of astrocytic MOR in different brain circuits and sexes.
