Health
Simple blood test diagnoses Parkinson's disease long before symptoms appear — A new research report appearing in the December issue of the FASEB Journal (http://www.fasebj.org) shows how scientists from the United Kingdom have developed a simple blood test to…
Early sign of Alzheimer's reversed in lab — One of the earliest known impairments caused by Alzheimer's disease - loss of sense of smell - can be restored by removing a plaque-forming protein in a mouse model of the disease,…
Parental controls on embryonic development? — When a sperm fertilises an egg, each contributes a set of chromosomes to the resulting embryo, which at these very early stages is called a zygote. Early on, zygotic genes are inert,…
Newly discovered heart stem cells make muscle and bone — Researchers have identified a new and relatively abundant pool of stem cells in the heart. The findings in the December issue of Cell Stem Cell, a Cell Press publication, show that…
BUSM researchers develop blood test to detect membranous nephropathy — Research conducted by a pair of physicians at Boston University School of Medicine (BUSM) and Boston Medical Centre (BMC) has led to the development of a test that can help diagnose…
New hip implants no better than traditional implants — New hip implants appear to have no advantage over traditional implants, suggests a review of the evidence published on bmj.com today…
Action needed to improve men's health in Europe — Policies aimed specifically at men are urgently needed to improve the health of Europe's men, say experts on bmj.com today…
Probiotics reduce infections for patients in intensive care — Traumatic brain injury is associated with a profound suppression of the patient's ability to fight infection. At the same time the patient also often suffers hyper-inflammation, due…
High blood sugar levels in older women linked to colorectal cancer — Elevated blood sugar levels are associated with an increased risk of colorectal cancer, according to a study led by researchers at Albert Einstein College of Medicine of Yeshiva University.…
Engineered botulism toxins could have broader role in medicine — The most poisonous substance on Earth - already used medically in small doses to treat certain nerve disorders and facial wrinkles - could be re-engineered for an expanded role in helping…
Where am I? > Home > News > Health

Compulsive behaviour in mice cured by bone marrow transplant

Science Centric | 28 May 2010 12:21 GMT
Printable version A clip for your blog or website E-mail the story to a friend
Bookmark or share the story on your social network Vote for this article Decrease text size Increase text size
DON'T MISS —
Loving the addict
Loving the addict — There's been a fair bit of study on people who are addicted, but what about the people who love and care for the addicted?…
Professor publishes 'Folktales of the Amazon'
Professor publishes 'Folktales of the Amazon' — As a boy living on a small farm with his grandparents in the Amazon region of Colombia, Juan Carlos Galeano was entranced…
More Health

Scientists earlier found that mice missing one of a group of core developmental genes known as the Hox genes developed an odd and rather unexpected pathology: the mutant animals groomed themselves compulsively to the point that they were removing their own hair and leaving self-inflicted open sores on their skin. Now, they've found a surprising connection between the Hoxb8 gene and the behaviour that looks an awful lot like that of people with an obsessive compulsive spectrum disorder (OCD).

Even more stunning, they report in the May 28th issue of Cell, a Cell Press publication, the animals' neuropsychological behaviour can be cured by bone marrow transplant.

It turns out that the Hoxb8 gene in question plays an important role in the development of immune cells known as microglia, which reside in the brain. Studies in which the researchers labelled Hoxb8 cells found that they show up in the brain exclusively in bone marrow-derived microglia. When they transplanted healthy bone marrow from control mice into the mutant animals, normal microglia made it to the animals' brains in about four weeks' time and many of the animals then stopped their incessant grooming, allowing their hair to grow back in, within three months of the procedure.

Those discoveries answered one big question 'Why a Hox gene?' according to the researchers. After all, microglia arise from haematopoietic stem cells in bone marrow before they reach their final destination in the brain and Hox genes are known to be heavily involved in haematopoietic cells, according to Mario Capecchi of Howard Hughes Medical Institute and University of Utah School of Medicine.

'But then, microglia and behaviour?' he asked. 'We would expect neurones to control behaviour - the circuitry of the brain - but then all of sudden we get this 'wild card' that microglia control behaviour.'

The classic job of microglia, which outnumber neurones in the brain, is to scan the brain for problems, he explained. When they find that something is wrong - maybe a pathogen has invaded or there has been a stroke - they change their shape to infiltrate the area and 'clean up the mess.' If you asked most any neuroscientist what microglia do, that's what they would probably tell you, Capecchi said.

In retrospect, he says, perhaps there were hints that microglia might be doing something more complicated. Fine processes that extend from the so-called resting microglia are always moving around in space. 'They can cover the whole brain space every hour,' he said. 'The processes randomly 'walk' around extending and protracting, scanning the brain. They are quite dynamic even when they are called 'resting.''

Others have recently shown that the cells move around and then suddenly stop at synapses (the connections between one neuron and the next). It appears that they stay at synapses that are active; otherwise, they simply wander away. 'It says that for some reason they are monitoring neural activity,' Capecchi said. 'But why monitor it if you aren't going to do something about it?'

Capecchi now thinks based on the new findings connecting microglia to OCD-like behaviours in mice that the immune cells might not only monitor neural behaviour but also modulate it, making sure it doesn't get out of hand. If they can't do their job properly, as in the Hoxb8 mutants, pathologies like the one they've seen in the mice may result.

Exactly how microglia might control brain activity is still anyone's guess, but the findings do add to evidence for a more general immune system role in mental disorders.

Capecchi notes that disorders such as depression, autism, Alzheimer's, and OCD do tend to be associated with immune deficiencies. But it wasn't really clear which came first. Genome-wide association studies in schizophrenia and OCD had also turned up genes involved in the immune system. But again, the connection wasn't entirely clear.

Capecchi said the new findings open the door to more detailed studies of how microglia and defects in microglia influence neural activity. They raise a host of other intriguing questions as well.

'Why couple behaviour such as grooming to the host's immune system?' the researchers ask in conclusion. 'From an evolutionary perspective it may make perfect sense to couple a behaviour such as grooming, whose purpose is to reduce pathogen count, with the cellular machinery - the innate and adaptive immune systems - used to eliminate pathogens,' they write.

'In summary,' they continue, 'we have provided strong support for the hypothesis that the excessive pathological grooming behaviour exhibited by Hoxb8 mutant mice is caused by a defect in microglia. That a behavioural deficit could be corrected by bone marrow transplantation is indeed surprising. The therapeutic implications of our study on amelioration of neurological behavioural deficits in humans have not escaped us.'

Capecchi said he wouldn't suggest a bone marrow transplant as a potential cure for mental disorders in humans today, given the significant risks associated with the procedure. But, as the saying goes, never say never.

Perhaps more importantly, he says, scientists still know a lot more about the immune system than they do about the brain. The new discovery suggests treatments 'that improve the immune system may have benefits for the brain,' he says. 'It opens up the spectrum of possibilities you can think about.'

Source: Cell Press


Leave a comment
The details you provide on this page [e-mail address] will not be used to send unsolicited e-mail, and will not be supplied to a third party! Please note that we can not promise to give everyone a response. Comments are fully moderated. Once approved they will be posted within 24 hours.
Expand the form to leave a comment

RSS FEEDS, NEWSLETTER
Find the topic you want. Science Centric offers several RSS feeds for the News section.

Or subscribe for our Newsletter, a free e-mail publication. It is published practically every day.

Scientists probe limits of 'cancer stem-cell model'Scientists probe limits of 'cancer stem-cell model'

— One of the most promising new ideas about the causes of cancer, known as the cancer stem-cell model, must be reassessed because it is based largely on evidence from…

An emergency brake in the brainAn emergency brake in the brain

— Brain researchers at the University of Oslo in Norway have penetrated deeply into the innermost secrets of the brain to find out how brain cells can survive a stroke.…

Timing is everything when it comes to childhood asthmaTiming is everything when it comes to childhood asthma

— Children who are born four months before the peak of cold and flu season have a greater risk of developing childhood asthma than children born at any other time…

Researchers at IRB Barcelona produce more data on key genes in diabetesResearchers at IRB Barcelona produce more data on key genes in diabetes

— One of the most reliable indicators to predict that a person will develop type 2 diabetes is the presence of insulin resistance. Insulin is produced in the pancreas…

Popular tags in Health: cancer · diabetes · malaria · obesity