Distinct and sex-specific expression of mu opioid receptors in anterior cingulate and somatosensory S1 cortical areas

Zamfir, Maria; Sharif, Behrang; Locke, Samantha; Ehrlich, Aliza T.; Ochandarena, Nicole; Scherrer, Grégory; Ribeiro‐da‐Silva, Alfredo; Kieffer, Brigitte L.; Séguéla, Philippe

doi:10.1097/j.pain.0000000000002751

Cited by 13 publications

(9 citation statements)

References 58 publications

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“…In addition, we confirmed that the astrocytic MOR in MOR-mCherry mice functions normally, as evidenced by the DAMGOinduced glutamate release in hippocampal astrocytes. This functional result is consistent with the previous evidence of intact MOR functionality in the MOR-mCherry reporter mouse which has shown normal expression, trafficking, TREK-1 colocalization, and MOR-mediated behavior responses [5,14,15]. We suggested the possibility that the expression of astrocytic MOR exhibits sex-differences in the brain regions.…”

Section: Discussionsupporting

confidence: 92%

“…The Oprm1 tm4Kff reporter mouse line (MOR-mCherry) [ 14 - 16 ], in which mCherry is tagged to the C-terminus of MOR, has been widely utilized to investigate MOR expression in neurons, due to the advantages of the unique transgenic property. Furthermore, this mouse line has confirmed the remaining functional MOR characteristics in MOR-mCherry mice, including normal Oprm1 gene transcription, proper distribution and trafficking of MOR-mCherry, comparable MOR agonist binding and potency, and conditioned place preference and pain-related behavioral responses as similar as observed in the wild-type mouse ( Oprm1 +/+ ) [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Mapping Astrocytic and Neuronal μ-opioid Receptor Expression in Various Brain Regions Using MOR-mCherry Reporter Mouse

Won,

Kim,

Shin

et al. 2023

Exp Neurobiol

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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.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Mapping Astrocytic and Neuronal μ-opioid Receptor Expression in Various Brain Regions Using MOR-mCherry Reporter Mouse

Won,

Kim,

Shin

et al. 2023

Exp Neurobiol

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“…Highly relevant for depression is the processing of both physical and psychological pain, where the ACC is relevant for the affective component [ 39 ]. The primary somatosensory cortex, on the other hand, is associated with the sensory-discriminative component [ 39 ] and increased rsFC between the thalamus and the SSC has been found in MDD, as compared to HC, which correlates with core symptom severity of MDD, such as cognitive dysfunction, anhedonia, etc. [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Functional Connectivity of the Anterior Cingulate Cortex and the Right Anterior Insula Differentiates between Major Depressive Disorder, Bipolar Disorder and Healthy Controls

et al. 2023

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Background: This study aimed to explore possible differences of the whole-brain functional connectivity of the anterior cingulate cortex (ACC) and anterior insula (AI), in a sample of depressed patients with major depressive disorder (MDD), bipolar disorder (BD) and healthy controls (HC). Methods: A hundred and three subjects (nMDD = 35, nBD = 25, and nHC = 43) between the ages of eighteen and sixty-five years old underwent functional magnetic resonance imaging. The CONN Toolbox was used to process and analyze the functional connectivity of the ACC and AI. Results: The comparison between the patients (MDD/BD) and HC yielded increased resting-state functional connectivity (rsFC) between the ACC and the motor and somatosensory cortices (SSC), superior parietal lobule (SPL), precuneus, and lateral occipital cortex, which was driven by the BD group. In addition, hyperconnectivity between the right AI and the motor and SSC was found in BD, as compared to HC. In MDD, as compared to HC, hyperconnectivity between ACC and SPL and the lateral occipital cortex was found, with no statistical rsFC differences for the AI seed. Compared to BD, the MDD group showed ACC–cerebellum hyperconnectivity and a trend for increased rsFC between the right AI and the bilateral superior frontal cortex. Conclusions: Considering the observed hyperconnectivity between the ACC/somatosensory cortex in the patient group, we suggest depression may be related to an impairment of the sensory-discriminative function of the SSC, which results in the phenomenological signature of mental pain in both MDD and BD. These findings suggest that future research should investigate this particular network with respect to motor functions and executive control, as a potential differential diagnostic biomarker for MDD and BD.

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“…A prominent finding in our research is the involvement of the anterior cingulate cortex (ACC) and more specifically the subcallosal area as well as the postcentral gyrus as differentiating components for MDD. The ACC has an extensive functional capacity with processing the affective component of pain ( 62 ) which is one of the more relevant in terms of the clinical presentation of depression. The postcentral gyrus, on the other hand, has been linked with the sensory-discriminative component of pain.…”

Section: Discussionmentioning

confidence: 99%

Degeneracy and disordered brain networks in psychiatric patients using multivariate structural covariance analyzes

Paunova,

Ramponi,

Kandilarova

et al. 2023

Front. Psychiatry

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IntroductionIn this study, we applied multivariate methods to identify brain regions that have a critical role in shaping the connectivity patterns of networks associated with major psychiatric diagnoses, including schizophrenia (SCH), major depressive disorder (MDD) and bipolar disorder (BD) and healthy controls (HC). We used T1w images from 164 subjects: Schizophrenia (n = 17), bipolar disorder (n = 25), major depressive disorder (n = 68) and a healthy control group (n = 54).MethodsWe extracted regions of interest (ROIs) using a method based on the SHOOT algorithm of the SPM12 toolbox. We then performed multivariate structural covariance between the groups. For the regions identified as significant in t term of their covariance value, we calculated their eigencentrality as a measure of the influence of brain regions within the network. We applied a significance threshold of p = 0.001. Finally, we performed a cluster analysis to determine groups of regions that had similar eigencentrality profiles in different pairwise comparison networks in the observed groups.ResultsAs a result, we obtained 4 clusters with different brain regions that were diagnosis-specific. Cluster 1 showed the strongest discriminative values between SCH and HC and SCH and BD. Cluster 2 had the strongest discriminative value for the MDD patients, cluster 3 – for the BD patients. Cluster 4 seemed to contribute almost equally to the discrimination between the four groups.DiscussionOur results suggest that we can use the multivariate structural covariance method to identify specific regions that have higher predictive value for specific psychiatric diagnoses. In our research, we have identified brain signatures that suggest that degeneracy shapes brain networks in different ways both within and across major psychiatric disorders.

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Distinct and sex-specific expression of mu opioid receptors in anterior cingulate and somatosensory S1 cortical areas

Abstract: Supplemental Digital Content is Available in the Text.Pain-processing anterior cingulate and primary somatosensory cortical areas display distinct MOR expression profiles with prominent differences between output layers and sexes.

Cited by 13 publications

References 58 publications

Mapping Astrocytic and Neuronal μ-opioid Receptor Expression in Various Brain Regions Using MOR-mCherry Reporter Mouse

Mapping Astrocytic and Neuronal μ-opioid Receptor Expression in Various Brain Regions Using MOR-mCherry Reporter Mouse

Functional Connectivity of the Anterior Cingulate Cortex and the Right Anterior Insula Differentiates between Major Depressive Disorder, Bipolar Disorder and Healthy Controls

Degeneracy and disordered brain networks in psychiatric patients using multivariate structural covariance analyzes

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