Microglia: a new target in the brain for depression, Alzheimer’s, autoimmune diseases

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Nov 5, 2011
Microglia: a new target in the brain for depression, Alzheimer’s, and more?

By Donna Jackson Nakazawa
January 17, 2020
Reactive region of the cerebral cortex showing the pervasiveness of neurofibrillary tangles (white), astrocytes (red), and microglia (green).

More than a decade ago, I was diagnosed with a string of autoimmune diseases, one after another, including a bone marrow disorder, thyroiditis, and then Guillain-Barré syndrome, which left me paralyzed while raising two young children.
I recovered from Guillain-Barré only to relapse, becoming paralyzed again. My immune system was repeatedly and mistakenly attacking my body, causing the nerves in my arms, legs, and those I needed to swallow to stop communicating with my brain, leaving me confined to — and raising my children from — bed.
As I slowly began to recover and learn to walk again, I noticed that along with residual physical losses I had experienced shifts in my mood and clarity of mind. Although I’d always been an optimistic person, I felt a bleak unshakable dread, which didn’t feel like the “old me.”
I also noticed cognitive glitches....
As a science journalist whose niche spans neuroscience, immunology, and human emotion, I knew at the time that it didn’t make scientific sense that inflammation in the body could be connected to — much less cause — illness in the brain. At that time, scientific dogma held that the brain was the only organ in the body not ruled by the immune system. The brain was considered to be “immune privileged.”
That began to change in the early 2010s. As neuroscience and immunology started to merge, they began dismantling that century-old tenet. Scientists pivoted away from believing that the brain and body function as church and state entities, and developed an entirely new brain-body paradigm which acknowledges that the brain is also governed by the immune system.
Much of the revelatory science fueling this reversal in how we see brain health was due to a radically new understanding of tiny cells called microglia. In healthy brains, microglia act as humble housekeepers, removing dead cells and bathing neurons in protective factors. A new understanding of these cells tells us that when they go rogue, they destroy synapses and cause inflammation in the brain.
In 2012, Beth Stevens, a young researcher at Children’s Hospital and Harvard Medical School, and her then-postdoc, Dori Schafer, discovered that microglia also determine synaptic health, for good or ill, from cradle to grave — a discovery for which Stevens was named a 2015 MacArthur “genius award” winner. They showed that these cells, which scientists had ignored since they were first noted in the 1920s, were actually powerful immune cells.
But just as the body’s immune system can rev into overdrive, causing inflammation and devastating physical symptoms, microglia can also become overexcited. When that happens, they can generate too much synaptic pruning, neuroinflammation, and symptoms of cognitive, mood, and behavioral disorders, from depression to Alzheimer’s disease.
This revelation, while scary to contemplate if you are a patient like me, is also the springboard for promise with a newly emerging and innovative set of tools that may help intervene in mental health disorders by treating the brain’s immune pathways much as we treat immune disorders of the body.
It turns out that people who have high levels of chronic inflammation, as measured by simple blood tests, also have higher levels of microglial activation in the brain, a keen and worrisome indicator that too many synapses are being lost....
...measuring individuals’ levels of inflammation ...
... infusions of ketamine ... appears to work as an anti-inflammatory in the brain. ...
... Of particular interest is how inflammation, which can signal microglia to become overactive and destroy synapses ...
... The hope is that by getting overexcited microglia to back off, important regions of the brain will be able to communicate again. ...
... When microglia go haywire, they destroy synapses and neural connections in the brain that affect mood and behavior. ...

- read more on statnews.com: Microglia: a new brain target for depression and Alzheimer's? - STAT

Donna Jackson Nakazawa is an award-winning journalist and internationally recognized speaker exploring the intersection of neuroscience, immunology and human emotion. She is the author of six books, including her latest, The Angel and the Assassin: The Tiny Brain Cell that Changed the Course of Medicine. Her mission is to translate the latest science to help those suffering from chronic conditions find hope and healing. : (Read an Excerpt): Donna Jackson Nakazawa

Donna Jackson Nakazawa blog: Donna Jackson Nakazawa

The Tiny Brain Cell That Changed the Course of Medicine
by Donna Jackson Nakazawa
About Donna page: About Donna


Level 69
Thread author
Nov 5, 2011
Glial Brain Cells, Long in Neurons’ Shadow, Reveal Hidden Powers
by Elena Renken
January 27, 2020
Glial astrocyte cell - AstrocyteBlog_thumb.jpg
The glial cells of the nervous system have been eclipsed in importance by neurons for decades. But glia are turning out to be central to many neurological functions, including pain perception

The sting of a paper cut or the throb of a dog bite is perceived through the skin, where cells react to mechanical forces and send an electrical message to the brain. These signals were believed to originate in the naked endings of neurons that extend into the skin. But a few months ago, scientists came to the surprising realization that some of the cells essential for sensing this type of pain aren’t neurons at all. It’s a previously overlooked type of specialized glial cell that intertwines with nerve endings to form a mesh in the outer layers of the skin. The information the glial cells send to neurons is what initiates the “ouch”: When researchers stimulated only the glial cells, mice pulled back their paws or guarded them while licking or shaking — responses specific to pain.
This discovery is only one of many recent findings showing that glia, the motley collection of cells in the nervous system that aren’t neurons, are far more important than researchers expected....
In addition, some glia are challenging to study because their fates are so entwined with those of neurons that it’s hard to learn about them separately. If researchers try to learn about the glia’s functions by knocking them out and observing the effects, the neurons they support will die along with them.

But the cells that have been the subjects of an especially strong spike in interest over the last decade or so are the ones called microglia.
Microglia were originally defined in four papers published in 1919 by Pío del Río-Hortega, but the study of them then stalled for decades, until finally picking up in the 1980s. Microglia research is now growing exponentially, said Amanda Sierra, a group leader at the Achucarro Basque Center for Neuroscience. The work is exposing how microglia respond to brain trauma and other injuries, how they suppress inflammation, and how they behave in the presence of neurodegenerative diseases. The cells “really are at the edge between immunology and neuroscience,” Sierra said.
Guy Brown, a professor of biochemistry at the University of Cambridge, was first drawn to microglia by their star shapes and dynamic movements, but it was their behavior that held his attention. In recent years, microglia have been found to mimic the macrophages of the immune system by engulfing threats to the brain such as cellular debris and microbes. Microglia also seem to go after obsolete synapses. “If you live-image them, you can see them eating neurons,” Brown said.
Neurons and glia cannot function independently: Their interactions are vital to the survival of the nervous system and the memories, thoughts and emotions it generates. But the nature of their partnership is still mysterious....

-read more on quantamagazine.org : Glial Brain Cells, Long in Neurons’ Shadow, Reveal Hidden Powers
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