Like in all of our organ systems, there are specialized cells that have specific roles. For example, microglia are non-neuronal cells found in the CNS. They are tissue macrophages that play a role in the innate immune system. Normally their job is to be on the look out for damaged neurons or infectious agents and engulf them. They can also secrete cytokines ,including hydrogen peroxide and nitrous oxide, which will can lead directly to cell death.
I recently read an article in Science discussing the importance of microglia in the undamaged brain. The purpose of this paper was to investigate whether microglia monitor synaptic function and if they are involved in synaptic maturation and elimination. First they went about using fluorescent labels to tag excitatory postsynaptic density and another fluorescent label to tag microglia processes. Their results showed an overlapping or colocalization of the fluorescent markers which indicates microglia engulfment of post synaptic activity.
These researchers then took this study a step further by knocking out a chemokine receptor usually present on microglia. Without this chemokine receptor, the microglia will not be able to become activated and fulfill their roles in the CNS. Their studies showed that KO mice for this chemokine receptor had a greater incidence of LTD (long term depression), an increase in postsynaptic material as well as a higher susceptibility to drug induced seizures.
This paper showed the important role microglia play in an undamaged or uninfected CNS. Microglia engulf and eliminate post-synaptic activity during development. Synaptic pruning is important because it is a way of weeding out inefficient synapses. If microglia are nonfunctional or cannot become activated than the CNS system will have efficient as well as inefficient synapses. These inefficient synapses can lead to a number of problems including LTD and an overall less developed brain.
The paper brings up an important point, that genetic variation in the chemokine receptor involved in activating microglia, may contribute to susceptibility of developmental disorders associated with altered synapses number. If researchers are able to understand this chemokine receptor gene, we may be able to provide therapies and treatments for debilitating neurological diseases.
References:
http://www.sciencemag.org.dml.regis.edu/content/333/6048/1456.full.pdf?sid=f519e898-8935-4cc5-9587-ad8be1fcd9d5
After reading this post I was interested in all of the roles that microglia play in the CNS. Glial cells were originally just thought to be support cells to neurons and didn't have much function outside of neurons. This was proven to be unfounded with the many parts that glial play in the CNS and PNS. Microglia cells specifically have been shown to play an important role in maintaining homeostasis (by negative feedback loops) in the CNS especially with invading micro-organisms, trauma, inflammation, ischaemia, brain tumors and neurodegeneration.
ReplyDeleteAs we know that the risk of neurodegeneration, trauma and ischaemia increases with old age, I'm interested to know if the activity and number of microglia increase with old age as well.
Georg W Kreutzberg (1996) Microglia: a sensor for pathological events in the CNS. Trends in Neurosciences, 19(8) 312-318.