immune system

Leave a comment Posted on Posts

Immune Disorders Tied to Mental Illness?

dscn4762

Wow! This is my pet hypothesis, that mental illness is caused by immunological factors, and may even be an auto-immune disease. Well here, ladies and gentlemen, a bone marrow transplant cures mice of compulsively pulling out their hair!

Compulsive hair pulling is akin to obsessive compulsive disorder and changing the mice’s immune system (bone marrow transplant) stops them from pulling out their hair.

Please can I get a bone marrow transplant? Please?

http://psychcentral.com/news/2010/06/01/immune-disorders-tied-to-mental-illness/14171.html

A provocative study using genetically altered mice finds a cause-and-effect link between the immune system and a psychiatric disorder.

Mario Capecchi, a Nobel Prize-winning geneticist, discovered that bone marrow transplants cure mutant mice who pull out their hair compulsively.

The study provides the first cause-and-effect link between immune system cells and mental illness, and points toward eventual new psychiatric treatments.

“We’re showing there is a direct relationship between a psychiatric disorder and the immune system, specifically cells named microglia that are derived from bone marrow” and are found in the brain, says Capecchi.

“There’s been an inference. But nobody has previously made a direct connection between the two.”

The findings – published in the journal Cell – should inspire researchers “to think about potential new immune-based therapies for psychiatric disorders,” says Capecchi, a 2007 Nobel laureate in physiology or medicine.

Capecchi and colleagues showed that pathological grooming and hair-pulling in mice – a disorder similar to trichotillomania (trick-o-til-o-MAY-nee-ah) in humans – is caused by a mutant Hoxb8 gene that results in defective microglia, which are immune system cells that originate in bone marrow and migrate from blood to the brain.

Microglia defend the brain and spinal cord, attacking and engulfing infectious agents.

Mice with pathological grooming appear to groom normally, but do so too often and for too long, leading to hair removal and self-inflicted skin wounds. The disease of pulling out head or body hair is common in humans; studies in seven international communities found trichotillomania affecting 1.9 to 2.5 of every 100 people.

In the key experiment, geneticist Shau-Kwaun Chen, Capecchi and colleagues transplanted bone marrow from normal mice into 10 mice that had a mutant Hoxb8 gene and compulsively pulled out their own chest, stomach and side fur.

As the transplant took hold during ensuing months, grooming behavior became normal, four mice recovered completely and the other six showed extensive hair growth and healing of wounds.

“A lot of people are going to find it amazing,” says Capecchi. “That’s the surprise: bone marrow can correct a behavioral defect.”

Nevertheless, “I’m not proposing we should do bone marrow transplants for any psychiatric disorder” in humans, he says.

Bone marrow transplants are expensive, and the risks and complications are so severe they generally are used only to treat life-threatening illnesses, including certain cancers and disabling autoimmune diseases such as lupus.

Capecchi says that mice with the mutant gene that causes pathological grooming now can be used to study the surprising connections between the immune system’s microglia cells and mental illness – and ultimately to produce new treatments.

“We think it’s a very good model for obsessive-compulsive disorder,” he says.

Source: University of Utah Health Sciences

Leave a comment Posted on Posts

It’s the Immune System!

DSCN5325

In normal brains, the number of synapses (connections between neurons where neurotransmitters act and brain activity takes place and nerve impulses and information is passes on) is pruned or  whittled down as the brain matures from the womb to adolescence. These synapses are eliminated by immune cells of the brain called microglia.

First the hypothesis that Schizophrenia is caused by activation of microglia which eat away at synapses in childhood or adolescence, leading to fewer synapses and this mental illness! An amazing paper about which I wrote a post (https://wordpress.com/post/bipolar1blog.wordpress.com/3623) C1q is a protein that tags the neuronal synapses, once a synapse is tagged, microglia (the immune cells of the brain) come and chomp it away, voila, no more synapse. The information that that one synapse was transmitting is now lost. If this happens to many, many, synapses, a lot of communication and information is lost. And this loss leads to schizophrenia!

Now the same observations about Alzheimer’s as well! Microglia are eating away too may synapses in areas of the brain that are key to memory. β Amyloid is a plaque of protein found to a much larger extent in the brains of people with Alzheimer’s. It is a deposit that is seen along neurons of people with Alzheimer’s. What this research team has found is that C1q in conjunction with the existence of β Amyloid plaques is what causes the microglia to eat up healthy synapses. This lead to destruction of brain cell connectivity, especially in the areas that house memory. So this process that happens naturally in the womb, somehow gets turned on later in life and causes pruning of connections in neurons which we need and leads to Alzheimer’s.

Again, it’s the immune system stupid!

http://www.sciencemag.org/news/2016/03/over-pruning-synapses-may-drive-early-stage-alzheimer-s-disease?utm_source=newsfromscience&utm_medium=facebook-text&utm_campaign=alzhapses-3346

Alzheimer’s may be caused by haywire immune system eating brain connections

More than 99% of clinical trials for Alzheimer’s drugs have failed, leading many to wonder whether pharmaceutical companies have gone after the wrong targets. Now, research in mice points to a potential new target: a developmental process gone awry, which causes some immune cells to feast on the connections between neurons.

“It is beautiful new work,” which “brings into light what’s happening in the early stage of the disease,” says Jonathan Kipnis, a neuroscientist at the University of Virginia School of Medicine in Charlottesville.

Most new Alzheimer’s drugs aim to eliminate β amyloid, a protein that forms telltale sticky plaques around neurons in people with the disease. Those with Alzheimer’s tend to have more of these deposits in their brains than do healthy people, yet more plaques don’t always mean more severe symptoms such as memory loss or poor attention, says Beth Stevens of Boston Children’s Hospital, who led the new work.

What does track well with the cognitive decline seen in Alzheimer’s disease—at least in mice that carry genes that confer high risk for the condition in people—is a marked loss of synapses, particularly in brain regions key to memory, Stevens says. These junctions between nerve cells are where neurotransmitters are released to spark the brain’s electrical activity.

Stevens has spent much of her career studying a normal immune mechanism that prunes weak or unnecessary synapses as the brain matures from the womb through adolescence, allowing more important connections to become stronger. In this process, a protein called C1q sets off a series of chemical reactions that ultimately mark a synapse for destruction. After a synapse has been “tagged,” immune cells called microglia—the brain’s trash disposal service—know to “eat” it, Stevens says. When this system goes awry during the brain’s development, whether in the womb or later during childhood and into the teen years, it may lead to psychiatric disorders such as schizophrenia, she says.

Stevens hypothesized that the same mechanism goes awry in early Alzheimer’s disease, leading to the destruction of good synapses and ultimately to cognitive impairment. Using two Alzheimer’s mouse models—each of which produces excess amounts of the β amyloid protein, and develops memory and learning impairments as they age—she and her team found that both strains had elevated levels of C1q in brain tissue. When they used an antibody to block C1q from setting off the microglial feast, however, synapse loss did not occur, the team reports today in Science.

To Stevens, that suggests that the normal mechanism for pruning synapses during development somehow gets turned back on again in the adult brain in Alzheimer’s, with dangerous consequences. “Instead of nicely whittling away [at synapses], microglia are eating when they’re not supposed to,” she says.

The group is now tracking these mice to see whether a drug that blocks C1q slows their cognitive decline. To determine whether elevated β amyloid can cause the C1q system to go haywire, Stevens and colleagues also injected a form of the protein which is known to generate plaques into the brains of normal mice and so-called knockouts that could not produce C1q because of a genetic mutation. Although normal mice exposed to the protein lost many synapses, knockouts were largely unaffected, Stevens says. In addition, microglia only went after synapses when β amyloid was present, suggesting that the combination of protein and C1q is what destroys synapses, rather than either element alone, she says, adding that other triggers, such as inflammatory molecules called cytokines, might also set the system off.

The findings contradict earlier theories which held that increased microglia and C1q activity were merely part of an inflammatory reaction to β amyloid plaques. Instead, microglia seem to start gorging on synapses long before plaques form, Stevens says. She and several co-authors are shareholders in Annexon Biosciences, a biotechnology company that will soon start testing the safety of a human form of the antibody the team used to block C1q, known as ANX-005, in people.

Such a central role for microglia in Alzheimer’s disease is “still on the controversial side,” says Edward Ruthazer, a neuroscientist at the Montreal Neurological Institute and Hospital in Canada. One “really compelling” sign that the mechanism is important in people would be if high levels of C1q in cerebrospinal fluid early on predicted developing full-blown Alzheimer’s later in life, he says. Still, he says, “it’s difficult to argue with the strength of the study’s evidence.”

Leave a comment Posted on Posts

Loneliness May Warp Our Genes, And Our Immune Systems

Loneliness. Sometimes I like to be alone, but I never like to be lonely. I am happiest surrounded by my loved ones, laughing, doing, cooking, like at thanksgiving just a few days ago. I am always talking about living in a community where all my family members are my neighbors. There is no one closer than family, but our Western culture espouses individualism, so much so that community and extended families are nonexistent. And that makes me feel alone. And being alone is really bad for us, we intuitively know this, during caveman days, being alone meant being eaten by lions, tigers, or bears! The article below also offers scientific proof about our immune systems, more prevalent illnesses, that explains why being alone feels bad and is bad for us. I love my family and my friends and I love to spend time with them, building community is also important. Long live human associations!

http://www.npr.org/sections/health-shots/2015/11/29/457255876/loneliness-may-warp-our-genes-and-our-immune-systems?utm_source=facebook.com&utm_medium=social&utm_campaign=npr&utm_term=nprnews&utm_content=2055

Loneliness has been linked to everything from heart disease to Alzheimer’s disease. Depression is common among the lonely. Cancers tear through their bodies more rapidly, and viruses hit them harder and more frequently. In the short term, it feels like the loneliness will kill you. A study suggests that’s because the pain of loneliness activates the immune pattern of a primordial response commonly known as fight or flight.

For decades, researchers have been seeing signs that the immune systems of lonely people are working differently. Lonely people’s white blood cells seem to be more active in a way that increases inflammation, a natural immune response to wounding and bacterial infection. On top of that, they seem to have lower levels of antiviral compounds known as interferons.

That seemed to provide a link to a lot of the poor health outcomes associated with loneliness, since chronic inflammation has been linked to everything from cancer to depression. The human body isn’t built to hold a high level of inflammation for years. “That explains very clearly why lonely people fall at increased risk for cancer, neurodegenerative disease and viral infections as well,” says Steve Cole, a genomics researcher at the University of California, Los Angeles, and lead author on the study published in the Proceedings of the National Academy of Sciences on Monday.

But it still doesn’t explain how or why loneliness could change our bodies. To find that out, Cole and his collaborators tracked 141 people over five years. Every year, the researchers measured how lonely the participants felt and took blood samples to track the activity of genes involved with immunity and inflammation. They also tracked concentrations of the hormone norepinephrine, one of the two main signals during the flight-or-fight response.

Cole noticed that when people felt lonesome, they had significantly higher levels of norepinephrine coursing through their blood. That could explain all the other immune changes that happen when people suffer from social isolation.

In a life-threatening situation, norepinephrine cascades through the body and starts shutting down immune functions like viral defense, while ramping up the production of white blood cells called monocytes. “It’s this surge in these pro-inflammatory white blood cells that are highly adapted to defend against wounds, but at the expense of our defenses against viral diseases that come from close social contact with other people,” Cole says.

At the same time, lonely people seem to be shutting down genes that would make their bodies sensitive to cortisol, which lowers inflammation. That ramps up the defensive inflammation response, Cole says.

Loneliness gif

Credit: Meredith Rizzo/NPR

Loneliness would hit the switch on a defense plan our bodies initiate in the face of mortal danger, Cole thinks, if isolation is somehow truly lethal. “At this point, my best guess was that loneliness really is one of the most threatening experiences we can have,” he says. “Though I didn’t think of loneliness as being that awful. It’s not pleasant, but not something my body should be getting all up in arms about.”

In the world of cubicles and studio apartments, loneliness is everywhere. We find it in both crowds and empty rooms. We change cities and lose friends. Even in marriage, people can be strangers to one another. But things were very different for our ancestors. When humans were evolving in a prehistoric environment, they banded together for food and for protection.

To be ostracized from your tribe was a death sentence, says Charles Raison, a psychiatrist at the University of Wisconsin, Madison who did not work on the study. “Literally they would die. There was no human way to live in isolation,” he says.

Being alone in the wild meant you could be mauled by animals or even other human beings. Then your body would need extra defenses against wounds and infection, but less protection against viruses you get from other people, like the flu. In that case, the stressful response to loneliness would simply be the body’s way of trying to survive exile.

But this fight-or-flight immune response is really nonspecific, says Turhan Canli, a neuroscientist at Stony Brook University in New York who was not involved with the study. Loneliness might not necessarily have to do with ancient survival, he says. Our bodies basically have one panic button, and any kind of adverse condition can trigger this response. “I think loneliness is a kind of psychological stress,” he says. “The change in the immune response is part of biological changes that come with a stress condition.”

What Canli finds really interesting about Cole’s results is that people who felt lonely one year had increased gene activity around inflammation and norepinephrine later on. And people who had increased inflammation felt lonelier the next year. “It’s a two-way street,” he said. “Loneliness predicted biological changes, and biological changes predicted changes in loneliness.”

So the shock of social isolation could fuel inflammation in the body. And the immune system may affect a region of the brain processing fear and anxiety. “Inflammation can change people’s experiences of the social world and what they’re thinking,” says Naomi Eisenberger, a neuroscientist at the University of California, Los Angeles, who was not involved with the study. That could make us more apprehensive about social interaction and lead to more isolation.

If the cycle continues, that could explain chronic isolation and the subsequent depression and illnesses plaguing the lonely. “There are things we can do to get out of a depressed or lonely state, but they’re not easy,” Cole says. “Part of the reason is because these negative psychological states develop some kind of molecular momentum.”

But that doesn’t mean the loop is permanent. “Inflammatory biology is one thing, but it’s not the only thing,” he says. All it does is push our proclivity for social activity one way or another. But loneliness is deep. It’s encoded in our genetics, and it’s not easy to shake.