Related Experiment Video

Updated: Aug 22, 2025

Magnetic Isolation of Microglial Cells from Neonate Mouse for Primary Cell Cultures
07:23

Magnetic Isolation of Microglial Cells from Neonate Mouse for Primary Cell Cultures

Published on: July 25, 2022

3.2K

Antagonization of OX1 Receptor Potentiates CB2 Receptor Function in Microglia from APPSw/Ind Mice Model

Iu Raïch1,2,3, Joan Biel Rebassa1,2,3, Jaume Lillo2,3

  • 1Molecular Neuropharmacology Laboratory, Department of Biochemistry and Physiology, School of Pharmacy and Food Science, Universitat de Barcelona, 08007 Barcelona, Spain.

International Journal of Molecular Sciences
|November 11, 2022
PubMed

Insights

Researchers found that OX1R antagonists can enhance the neuroprotective effects of CB2R activation in microglia, suggesting a new therapeutic strategy for Alzheimer's disease (AD). This involves targeting CB2-OX1 receptor complexes, which are overexpressed in AD models.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Cell Biology

Background:

  • Orexin (OX) may regulate amyloid beta peptide (Aß) levels in Alzheimer's disease (AD).
  • Cannabinoid receptor 2 (CB2R) is upregulated in microglia and exerts neuroprotective effects.
  • CB2R and OX1R may form heteromers (CB2-OX1-Hets), presenting a novel therapeutic target for AD.

Purpose of the Study:

  • To investigate the expression and function of CB2-OX1 receptor heteromers in microglia from AD animal models.
  • To determine the structural and functional characteristics of the CB2-OX1 heteromer.
  • To evaluate the therapeutic potential of targeting this complex in AD.

Main Methods:

  • Immunocytochemistry, bioluminescence resonance energy transfer (BRET), and proximity ligation assay (PLA) for heteromer detection.
  • AlphaScreen®, western blot, GCaMP6 calcium sensor, and Lance Ultra cAMP assay for signal transduction analysis.
  • Utilized transfected HEK-293T cells, primary microglia cultures, and the APPSw/Ind AD mouse model.

Main Results:

  • Demonstrated the formation of a tetrameric CB2-OX1 receptor complex involving Gαi and Gαq proteins.
  • Identified the TM4-TM5 interface of the CB2-OX1 receptor complex.
  • Showed that OX1R antagonists potentiate CB2R agonist activity in both cell systems and microglia, with increased complex expression in AD models.

Conclusions:

  • The CB2-OX1 receptor complex is overexpressed in microglia of AD animal models.
  • OX1R antagonists enhance the neuroprotective effects of CB2R activation via this complex.
  • OX1R antagonists represent a promising therapeutic strategy for combating Alzheimer's disease.
Keywords:
Alzheimer’s diseaseactivated microgliacannabinoidsorexin

More Related Videos

Development of an Insert Co-culture System of Two Cellular Types in the Absence of Cell-Cell Contact11:29

Development of an Insert Co-culture System of Two Cellular Types in the Absence of Cell-Cell Contact

Published on: July 17, 2016

28.0K
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates09:12

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates

Published on: January 30, 2014

16.1K

Related Concept Videos

Opioid Receptors: Overview01:22

Opioid Receptors: Overview

Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2,...
1.5K
Combined Effects of Drugs: Antagonism01:30

Combined Effects of Drugs: Antagonism

The combined effects of drugs can result in various interactions, of which an important type is antagonism. Antagonism is a mechanism where one drug inhibits or counteracts the effects of another drug. Antagonism can occur through various means, including receptor binding, allosteric modulation, functional interaction, chemical reactions, and pharmacokinetic processes.
The most common type is receptor antagonism, where one drug acts as an antagonist to block the effects of another drug by...
9.1K
Agonism and Antagonism: Quantification01:14

Agonism and Antagonism: Quantification

When drugs are administered, they can elicit either an agonist or antagonist effect on the body. Agonism occurs when a drug activates a specific receptor, triggering a biological response. On the other hand, antagonism happens when a drug binds to the same receptors but blocks their activation, thereby preventing a biological response.
To quantify these effects, researchers use a dose-response curve, which provides valuable information about the potency and efficacy of a drug. Potency refers to...
500
Drug-Receptor Interaction: Agonist01:25

Drug-Receptor Interaction: Agonist

Agonists are drugs that interact with specific receptors in the body to produce a biological response. When an agonist binds to a receptor, it activates or enhances the receptor's function, leading to physiological effects. The interaction between agonist drugs and receptors is crucial for their therapeutic action in various medical treatments.
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous...
2.7K