An Introduction to Microglia in the Aging Brain

Microglia are immune cells that defend and clean up the brain and spinal cord. Like the rest of the immune system, they progressively fail in their work with age. Worse, like other immune system components, they begin to become actively harmful by causing chronic inflammation and other forms of damage instead of helping. Reversing that trend is one important line of research among many that, as they produce working medical technologies, will extend our healthy life spans.

Keeping the brain in good working shape is one of the most important goals of medical research. There is no short cut here by way of the comparatively advanced fields of stem cell medicine and tissue engineering - we can't look ahead to replacement brains in the next decade or two as we can for other organs. The brain has to be repaired in situ, completely and sufficiently for the long term: every form of age-related cellular damage either worked around or reversed. So microglia, as an important part of the existing maintenance systems in the brain, are of considerable interest. Can early successes be obtained by boosting their activity, or slowing or reversing their decline with age? The Longecity-funded research project on microglia transplants falls into this general area of research - something we'd like to see more of.

Following on from that topic, here is an open access review paper that provides an introduction to microglia in context of aging and neurodegeneration:

For many years, chronic neurodegenerative disorders of the central nervous system (CNS) were thought of in terms of primary neuronal dysfunction and loss with secondary glial and inflammatory responses. ... but of late this theory has required revision.

Microglia, which account for approximately 10% of the adult brain cell population, were first described by Pio Del Rio Hortega in 1919 ... However, it was not until the late 1980s that this field came of age when, using the new technique of immunohistochemistry, the McGeers showed that within the Alzheimer's disease (AD) brain there were large numbers of [activated] microglia. ... The pioneering work of the McGeers was to radically change how these diseases were seen as they went on to show that microglia were not only intimately bound to central inflammatory responses and antigen presentation, but in fact the whole innate immune system itself had a role to play in these CNS disorders.

Initial views on the role of microglia suggested that these cells were simply there to scavenge up debris and dead cells, while astrocytes fulfilled some supportive role in the CNS. However, microglia are now recognized to have a complex array of supportive and destructive roles in the CNS and that the balance between the two may be critical in driving some aspects of disease processes. Astrocytes are now seen as being fundamental in shaping and maintaining the developing and mature CNS, including a role in adult neurogenesis, axonal regeneration, and the [blood-brain barrier]. The dynamic interplay between all of these different CNS compartments is becoming more evident, such that some neurodegenerative disorders of the CNS may have a pathology as much in the glial cells as in the neurons themselves. This all means that understanding what happens in disease states is far more complex than originally conceived and that targeting each element of the interaction may be the route by which true disease modification can be achieved.


...and not forgetting the potential importance of senescent microglia in the ageing/diseased brain.

Posted by: c0zmic at June 6th, 2012 2:09 AM

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