Textbooks redefined as microglia seen entering the Peripheral Nervous System.

All of our thoughts, bodily functions, memories, and senses are controlled by the central nervous system (CNS), consisting of the brain and spinal cord. Inside the CNS it is the job of neuroimmune cells called microglia, to clean up cellular debris with their counterparts macrophages.

These macrophages or white blood cells are known to serve similar functions in the peripheral nervous system (PNS), the region outside of the brain containing most of the sensory and motor nerves.  It has long been believed microglia are restricted to the CNS, unable to travel to the PNS. 

Now, a study from researchers at the University of Notre Dame shows microglia actually squeeze through the spinal boundary, crossing into the peripheral nervous system in response to injury.  The team states their study could have broad implications in the area of nervous system diseases. Likewise, the data could open the door to a completely new set of questions in the study of both systems.  The opensource study is published in the journal PLOS Biology.

Microglia do not stay in the brain

Previous studies show microglia have a growing list of functions, including synaptic pruning and clearance of debris in the CNS.  During these processes, microglia change into what is known as an activated or altered state. This in turn leads to increased cellular migration and phagocytic activity, which can produce lasting impacts on the nervous system. 

Despite the growing list of functions of microglia to the CNS, little is known about their role outside of the CNS domain.  The current study uses time-lapse imaging in a spinal cord injury model to show microglia squeeze through the spinal boundary and emigrate to peripheral spinal roots, in effect the PNS.

The current study models a brachial plexus injury in zebrafish spinal cords to observe how microglia and macrophages respond. Brachial plexus injuries take place at the intersection of the central and peripheral nervous systems. Subsequently affecting nerves connecting the CNS to the shoulders, arms, and hands. 

Results show microglia squeeze through the spinal boundary, crossing into the PNS in response to injury.  Data findings show once inside the PNS microglia do their job of clearing cellular debris at the point of injury. However, they actually return to the CNS with this debris, and could potentially carry it straight to the brain.

The team explains they observed the microglia returning to the CNS in an altered state. Importantly, altered microglia is implicated in countless neurodegenerative diseases, as well as the autism spectrum disorder. 

Microglia cause damage in the PNS

Comparatively, they go on to add altered microglial cells can clear too much cellular material, including material they normally do not clear, in the brain. Consequently, this potentially causes neuropathic pain or disease-type states, as the cells are clearing or removing cellular material necessary for the nervous system to function correctly.

The team surmises they provide evidence microglia function expands beyond their textbook-defined CNS-resident domain into the PNS.  For the future, the researchers state it is imperative that research begins on microglia migration to the PNS in the pathology of neurological disease and disorders.

Source: University of Notre Dame

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