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Unexpected Microglial "De-activation" Associated With Altered Synaptic Transmission in the Early Stages of an Animal
Shaona Acharjee1, Quentin J Pittman1
1Department of Physiology & Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
Abstract:
Multiple sclerosis, and its animal model-experimental autoimmune encephalomyelitis (EAE), is a demyelinating disease causing motor and sensory dysfunction, as well as behavioral comorbidities. In exploring possible functional changes underlying behavioral comorbidities in EAE, we observed increased excitatory drive onto the major cells of the basolateral amygdala. This was associated with increased numbers of dendritic spines. An unexpected finding was that microglial cells at this time were in a "deactivated" state, and further studies suggested that the microglial deactivation was responsible for the increased excitatory drive. This is the first report of microglial deactivation in an inflammatory disease and raises many questions as to the underlying mechanisms and functional relevance.
Insights
In experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, researchers found deactivated microglia increased excitatory drive in the brain. This surprising finding links microglial state to neurological dysfunction in inflammatory diseases.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are characterized by demyelination, leading to motor, sensory, and behavioral deficits.
- Behavioral comorbidities in EAE suggest underlying functional changes in neural circuits.
- The basolateral amygdala is implicated in emotional and behavioral regulation.
Purpose of the Study:
- To investigate functional neural changes associated with behavioral comorbidities in EAE.
- To explore the role of microglial cells in the observed neurological alterations during EAE.
Main Methods:
- Induction of EAE in a preclinical model.
- Electrophysiological recordings in the basolateral amygdala to assess neuronal activity.
- Dendritic spine density analysis.
- Immunohistochemical analysis of microglial states.
Main Results:
- EAE induction led to increased excitatory drive onto principal neurons in the basolateral amygdala.
- A significant increase in dendritic spine density was observed in these neurons.
- Unexpectedly, microglial cells in the affected brain regions were found in a deactivated state.
- Further investigation suggested a causal link between microglial deactivation and enhanced excitatory drive.
Conclusions:
- Microglial deactivation, not activation, is associated with increased excitatory drive in the basolateral amygdala during EAE.
- This represents the first report of microglial deactivation in an inflammatory neurological disease.
- The findings challenge conventional roles of microglia in neuroinflammation and suggest novel mechanisms underlying behavioral comorbidities in MS.