Compulsive Disorder in Mice can be Cured by Transplanting Bone Marrow

New research says that compulsive behaviour in mice can be cured by bone marrow transplant. The study has appeared in the May 28th issue of Cell, a Cell Press publication.

The Hoxb8 gene 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 hematopoietic stem cells in bone marrow before they reach their final destination in the brain and Hox genes are known to be heavily involved in hematopoietic cells, according to Mario Capecchi of Howard Hughes Medical Institute and University of Utah School of Medicine.

Advertisement

He said: "But then, microglia and behavior?

"We would expect neurons to control behavior - the circuitry of the brain - but then all of sudden we get this 'wild card' that microglia control behavior."

Advertisement

The classic job of microglia, which outnumber neurons 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," 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.

He said: "They can cover the whole brain space every hour.

"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.

Capecchi said: "It says that for some reason they are monitoring neural activity.

"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 behaviours 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.

The authors write: "In summary 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."

Source-ANI
RAS