Dynamic Responses of Microglia in Animal Models of Multiple Sclerosis
Melanie J Plastini1,2, Haritha L Desu1,2, Roberta Brambilla1,2,3,4
1The Miami Project To Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, United States.
Abstract:
Microglia play an essential role in maintaining central nervous system (CNS) homeostasis, as well as responding to injury and disease. Most neurological disorders feature microglial activation, a process whereby microglia undergo profound morphological and transcriptional changes aimed at containing CNS damage and promoting repair, but often resulting in overt inflammation that sustains and propagates the neurodegenerative process. This is especially evident in multiple sclerosis (MS), were microglial activation and microglia-driven neuroinflammation are considered key events in the onset, progression, and resolution of the disease. Our understanding of microglial functions in MS has widened exponentially in the last decade by way of new tools and markers to discriminate microglia from other myeloid populations. Consequently, the complex functional and phenotypical diversity of microglia can now be appreciated. This, in combination with a variety of animal models that mimic specific features and processes of MS, has contributed to filling the gap of knowledge in the cascade of events underlying MS pathophysiology. The purpose of this review is to present the most up to date knowledge of the dynamic responses of microglia in the commonly used animal models of MS, specifically the immune-mediated experimental autoimmune encephalomyelitis (EAE) model, and the chemically-induced cuprizone and lysolecithin models. Elucidating the spectrum of microglial functions in these models, from detrimental to protective, is essential to identify emerging targets for therapy and guide drug discovery efforts.
Insights
Microglia activation in multiple sclerosis (MS) involves complex changes that can both harm and heal the central nervous system (CNS). Understanding these dynamic microglial responses in MS models is key for developing new therapies.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Microglia are crucial for central nervous system (CNS) homeostasis and disease response.
- Microglial activation in neurological disorders, particularly multiple sclerosis (MS), contributes to neuroinflammation and neurodegeneration.
- Recent advancements in tools and animal models have significantly enhanced our understanding of microglial diversity and function in MS.
Purpose of the Study:
- To review current knowledge on dynamic microglial responses in established animal models of MS.
- To explore the spectrum of microglial functions, from detrimental to protective, in MS pathogenesis.
- To identify potential therapeutic targets for MS based on microglial behavior.
Main Methods:
- Review of literature on microglial responses in animal models of MS.
- Focus on experimental autoimmune encephalomyelitis (EAE), cuprizone, and lysolecithin models.
- Analysis of morphological and transcriptional changes in microglia.
Main Results:
- Microglial activation is a central event in MS, exhibiting diverse roles in disease onset, progression, and resolution.
- Animal models reveal a spectrum of microglial functions, highlighting both pro-inflammatory and protective activities.
- Distinguishing microglia from other myeloid cells is critical for understanding their specific contributions.
Conclusions:
- Elucidating the dual role of microglia in MS pathogenesis is essential for therapeutic development.
- Targeting specific microglial functions offers promising avenues for novel MS therapies.
- Further research into microglial dynamics in MS models will guide future drug discovery efforts.
