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Exploring the role of microglia in mood disorders associated with experimental multiple sclerosis
Antonietta Gentile1, Francesca De Vito1, Diego Fresegna1
1Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC) Rome, Italy ; Clinica Neurologica, Dipartimento di Medicina dei Sistemi, Università Tor Vergata Rome, Italy.
Abstract:
Microglia is increasingly recognized to play a crucial role in the pathogenesis of psychiatric diseases. In particular, microglia may be the cellular link between inflammation and behavioral alterations: by releasing a number of soluble factors, among which pro-inflammatory cytokines, that can regulate synaptic activity, thereby leading to perturbation of behavior. In multiple sclerosis (MS), the most common neuroinflammatory disorder affecting young adults, microglia activation and dysfunction may account for mood symptoms, like depression and anxiety, that are often diagnosed in patients even in the absence of motor disability. Behavioral studies in experimental autoimmune encephalomyelitis (EAE), the animal model of MS, have shown that emotional changes occur early in the disease and in correlation to inflammatory mediator and neurotransmitter level alterations. However, such studies lack a full and comprehensive analysis of the role played by microglia in EAE-behavioral syndrome. We review the experimental studies addressing behavioral symptoms in EAE, and propose the study of neuron-glia interaction as a powerful but still poorly explored tool to investigate the burden of microglia in mood alterations associated to MS.
Insights
Microglia, immune cells in the brain, are linked to psychiatric conditions. Their dysfunction in multiple sclerosis (MS) may cause mood changes like depression and anxiety.
Area of Science:
- Neuroscience
- Immunology
- Psychiatry
Background:
- Microglia play a key role in psychiatric disease pathogenesis.
- Microglia dysfunction and activation are implicated in mood disorders like depression and anxiety, particularly in neuroinflammatory conditions such as multiple sclerosis (MS).
- In experimental autoimmune encephalomyelitis (EAE), the animal model for MS, emotional changes correlate with inflammatory mediator and neurotransmitter alterations.
Purpose of the Study:
- To comprehensively analyze the role of microglia in the behavioral syndrome observed in EAE.
- To review existing experimental studies on behavioral symptoms in EAE.
- To highlight neuron-glia interactions as a critical area for understanding microglia's contribution to MS-related mood alterations.
Main Methods:
- Review of experimental studies investigating behavioral symptoms in EAE.
- Analysis of the literature on microglia activation and dysfunction in the context of MS and EAE.
- Exploration of the relationship between inflammation, neurotransmitters, and behavior in EAE.
Main Results:
- Microglia activation and dysfunction are associated with mood symptoms in MS patients, even without motor deficits.
- Behavioral changes in EAE models occur early and correlate with neurochemical alterations.
- Existing studies often lack a comprehensive analysis of microglia's specific role in EAE-associated behavioral changes.
Conclusions:
- Microglia are central to the link between inflammation and behavioral alterations in psychiatric diseases.
- Investigating neuron-glia interactions offers a promising avenue to understand microglia's impact on mood disorders in MS.
- Further research is needed to fully elucidate the burden of microglia in MS-related mood alterations.
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