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Updated: May 12, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Modulation of ageing mice microglia functions during neuroinflammation using synthetic cannabinoids
Akshay Kumar Vijaya1, Greta Krisikaitytė1, Simonas Kuras1
1Department of Biological Models, Institute of Biochemistry, Life Sciences Center, Vilnius University, Sauletekio Ave. 7, LT-10257, Vilnius, Lithuania.
Abstract:
Ageing is marked by a gradual rise in systemic inflammation, with neuroinflammation being a key feature. Neuroinflammation, which refers to the immune response within the CNS, is primarily mediated by microglia. These resident macrophages in the CNS parenchyma are essential for maintaining homeostasis and initiating immune responses. Their function depends on the timely activation and deactivation of microglia to regulate these processes effectively. Excessive activation of microglia has been shown to disrupt brain functions and promote a proinflammatory response leading to dysfunctional microglia that are unable to carry out immune response due to various reasons, with major implications in neuroinflammation. Therefore, there is a need to monitor and modulate the functionality of microglia to elicit a healthy immune response. The endocannabinoid system is a negative feedback system that is activated to modulate various mechanisms related to inflammation. In our research, we therefore investigated the functionality of microglia in relation to phagocytosis and oxidative stress during neuroinflammation by stimulating the endocannabinoid receptors Cnr1 and Cnr2 with synthetic cannabinoid compounds in ageing mice. Our results show that the expression of the endocannabinoid system (ECS) increases with age. Activation of CB1 and CB2 receptors reduces reactive oxygen species (ROS) in both young and aged mice, with the effect being more pronounced effect in younger mice. In aged mice, the upregulation of these receptors indicates persistent inflammation, while microglial phagocytosis is modulated through CB1 receptors in both age groups.
Insights
As we age, neuroinflammation increases, impacting microglial function. Activating endocannabinoid receptors (CB1/CB2) with cannabinoids reduces oxidative stress and modulates microglial phagocytosis, offering potential therapeutic avenues.
Area of Science:
- Neuroscience
- Immunology
- Aging Research
Background:
- Aging is associated with increased systemic inflammation and neuroinflammation.
- Microglia, the brain's immune cells, are crucial for CNS homeostasis and immune responses.
- Dysfunctional microglia contribute to neuroinflammation and impaired brain function.
Purpose of the Study:
- To investigate microglial functionality (phagocytosis, oxidative stress) during neuroinflammation in aging mice.
- To explore the role of the endocannabinoid system (ECS) in modulating microglial responses.
- To assess the effects of synthetic cannabinoid compounds targeting CB1 and CB2 receptors.
Main Methods:
- Utilized aging mice models.
- Stimulated cannabinoid receptors (Cnr1 and Cnr2) using synthetic cannabinoid compounds.
- Assessed microglial phagocytosis and oxidative stress (reactive oxygen species - ROS).
Main Results:
- Endocannabinoid system (ECS) expression is upregulated with age.
- CB1 and CB2 receptor activation reduced ROS in young and aged mice, more significantly in younger mice.
- Microglial phagocytosis was modulated by CB1 receptor activation across age groups.
- Upregulation of CB1/CB2 receptors in aged mice suggests persistent inflammation.
Conclusions:
- The endocannabinoid system plays a role in regulating microglial function during neuroinflammation.
- Cannabinoid receptor activation shows potential for mitigating oxidative stress and modulating microglial activity.
- Targeting the ECS may offer a strategy for managing age-related neuroinflammation and microglial dysfunction.
