Textbooks redefined as microglia seen entering the Peripheral Nervous System.
Inside the central nervous system (CNS), a region that includes the brain and spinal cord, it is the job of neuroimmune cells called microglia, to clean up cellular debris. Microglia have counterparts called macrophages that serve similar function outside the CNS in the peripheral nervous system (PNS), the region that contains most of the sensory and motor nerves. It has long been believed that microglia are restricted to the CNS, unable to travel to the PNS. Now, a study from researchers at the University of Notre Dame shows that microglia actually squeeze through the spinal boundary, crossing into the peripheral nervous system in response to injury. The team state their study could have broad implications in the area of nervous system diseases, while opening 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.
Previous studies show that 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, leading 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 chord injury model to show that 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 chords to observe how microglia and macrophages respond. Brachial plexus injuries take place at the intersection of the central and peripheral nervous systems, 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 that once inside the PNS microglia do their job of clearing cellular debris at the point of injury, however, they return to the CNS with that debris, and could potentially carry it straight to the brain.
The team explain they observed the microglia returning to the CNS in an altered state, with altered microglia implicated in countless neurodegenerative diseases, as well as autism spectrum disorder. They go on to add that altered microglial cells can clear too much cellular material, including material they normally do not clear, in the brain, potentially causing neuropathic pain, disorder or disease-type states, as the cells are clearing or removing cellular material that’s necessary for proper nervous system function.
The team surmise they provide evidence that microglia function expands beyond their textbook-defined CNS-resident domain into the PNS. For the future, the researchers state it is imperative that research begin on microglia migration to the PNS in the pathology of neurological disease and disorders.
Source: University of Notre Dame