Studies on mice suggests that some psychological disorders may be treated by boosting the immune system.
Credit: Science Museum, UK
SYDNEY: What if mental disorders such as Alzheimer’s and obsessive-compulsive disorder could be treated by boosting the immune system? A study in mice suggests it may be possible.
This idea may not be so far fetched, thanks to geneticists at the Howard Hughes Medical Institute in Chicago and the University of Utah School of Medicine who have cured obsessive-compulsive disorder (OCD) in mice by giving them a bone marrow transplant.
Mutated immune cells that originated in the bone marrow were found to be the switch to turn this disease on and off.
“We initially had this mouse that had this [unusual grooming behaviour], then the question is, why does it have this behaviour?” said Mario Capecchi of the University of Utah, 2007 Nobel laureate in medicine and lead author of a paper in the journal Cell.
“We assumed something was the matter with the brain, [and that’s what] caused the behaviour to be defective,” he added.
Mutations of a Hox gene
The team studied a group of mice, all of which displayed OCD-like behaviours, grooming excessively, pulling their hair out and leaving exposed patches of skin and open sores. These mice also shared another common trait- they all had mutations of a gene called Hoxb8.
By labelling the causal genes with green, yellow and blue colour markers, they found Hoxb8 in cells called microglia, immune system cells that operate in the brain.
These results were particularly surprising because it was commonly thought that brain nerve cells, not immune system cells, were associated with controlling grooming behaviours. Microglia cells were thought to have more of a damage remediation role in the brain.
Because they knew that microglia originate in the bone marrow before migrating to the brain, the group predicted that if they gave the mice with OCD a bone marrow transplant - effectively replacing the defective microglia cells with unmutated ones - the mice could be cured of their OCD behaviour.
“If you’d told anybody that before, they’d say you’re crazy! But it works, and it works very efficiently,” noted Capecchi.
“If you look at [the patients of] any psychiatric disease … they often have defects in the immune system. The cause and effect wasn’t clear,” he said.
Transplant of bone marrow
The team took four groups of 10 mice: two groups with OCD behaviours, and two without. One group of each mutant and non-mutant mice were given a transplant of bone marrow from non-OCD mice, and the other groups were transplanted with bone marrow from non-OCD mice.
The group of OCD mice transplanted with the non-OCD bone marrow appeared to be cured- over the following months; four mice recovered completely; and the other six showed hair regrowth and healing. The six mice with lessened symptoms may be just be healing slower, according to Capecchi.
The OCD mice transplanted with the OCD bone marrow had symptoms that appeared to worsen.
Similarly, normal mice grafted with the bone marrow from OCD mice began to exhibit obsessive grooming behaviour. Meanwhile normal mice transplanted with normal bone marrow showed no change in behaviour.
This immune system/psychological disorder linkage may be a key component in developing possible treatments or cures for afflicted humans in the future, said Capecchi.
“The reason it’s important is because we know a lot more about our immune system than our brain,” he said. Likewise, we know a lot more about the functionality and targets of drugs for the immune system than in neuro-psychotic drugs.
Immune system link
And, an immune system linked with grooming behaviours, both in mice and in humans, makes evolutionary sense, according to the researchers. Grooming in mice, like some OCD behaviours in humans - such as hand washing and obsession over germs - rid the body of potential pathogens.
“Essentially they’re doing the same thing, so wouldn’t it make sense that you couple your behaviour with the system that’s trying to actually kill the pathogens?” asked Capecchi.
Mark Hill, a researcher at the University of New South Wales in Sydney who has worked with Hox genes was intrigued. “There are many people who have been looking at microglia for their other roles,” he said. “These findings indicate a novel role, from what they’ve been previously identified as.”
Now the researchers are working to determine what behaviours could come about with an abundance of un-mutated microglial cells in mice, and the prediction is that they should groom less or have an aversion to grooming.
As for prevention, a Vitamin C drop or an immune-boosting smoothie might be a good first line of prevention against psychological illness. “I take lots of Vitamin C," Capecchi said. "It’s not likely to hurt, and it may help- anything that stimulates the immune system may help.”
