Microglial process convergence on axonal segments in health and disease
Savannah D Benusa1, Audrey D Lafrenaye1
1Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Abstract:
Microglia dynamically interact with neurons influencing the development, structure, and function of neuronal networks. Recent studies suggest microglia may also influence neuronal activity by physically interacting with axonal domains responsible for action potential initiation and propagation. However, the nature of these microglial process interactions is not well understood. Microglial-axonal contacts are present early in development and persist through adulthood, implicating microglial interactions in the regulation of axonal integrity in both the developing and mature central nervous system. Moreover, changes in microglial-axonal contact have been described in disease states such as multiple sclerosis (MS) and traumatic brain injury (TBI). Depending on the disease state, there are increased associations with specific axonal segments. In MS, there is enhanced contact with the axon initial segment and node of Ranvier, while, in TBI, microglia alter interactions with axons at the site of injury, as well as at the axon initial segment. In this article, we review the interactions of microglial processes with axonal segments, analyzing their associations with various axonal domains and how these interactions may differ between MS and TBI. Furthermore, we discuss potential functional consequences and molecular mechanisms of these interactions and how these may differ among various types of microglial-axonal interactions.
Insights
Microglia interact with axons, impacting neuronal networks and axonal integrity. These interactions change in diseases like multiple sclerosis and traumatic brain injury, affecting specific axonal regions.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Microglia are key immune cells in the central nervous system.
- Microglia dynamically interact with neurons, influencing network development and function.
- Emerging evidence suggests microglia physically interact with axonal domains, potentially modulating neuronal activity.
Purpose of the Study:
- To review microglial process interactions with axonal segments.
- To analyze associations with various axonal domains.
- To explore differences in these interactions in multiple sclerosis (MS) and traumatic brain injury (TBI).
Main Methods:
- Literature review of studies on microglial-axonal interactions.
- Analysis of microglial contact with specific axonal segments (axon initial segment, node of Ranvier).
- Comparison of interaction patterns in development, adulthood, MS, and TBI.
Main Results:
- Microglial-axonal contacts are present from development through adulthood.
- Disease states like MS and TBI show altered microglial-axonal contacts.
- MS involves enhanced contact at the axon initial segment and node of Ranvier; TBI alters contacts at injury sites and the axon initial segment.
Conclusions:
- Microglial-axonal interactions play a role in regulating axonal integrity in both health and disease.
- Understanding these interactions is crucial for deciphering their functional consequences and molecular mechanisms in neurological disorders.
- Differential microglial-axonal engagement in MS and TBI highlights disease-specific roles.
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