UAB offers new research into brain, spinal cord disease

on March 13, 2012 at 7:30 AM
UAB logo 2-19-12.JPG

New UAB research describes a potentially useful model of some human neurological disease -- including multiple sclerosis, an autoimmune disease that affects the brain and spinal cord.

In a paper published Monday in Proceedings of the National Academy of Sciences, a team of researchers led by Dr. Hongwei Qin and Etty "Tika" Benveniste reports on a genetically altered line of black mice, whose myeloid immune cells no longer produce a protein called SOCS3.

The researchers suspected that loss of this gene would have an impact on autoimmune disease, and results were more dramatic than expected.

In the common lab model of multiple sclerosis, this is what happens. Mice are given a compound called MOG. This causes an inflammatory response in the mice that attacks their nerve cells. By day 10, they start to get paralysis of their tails, and that paralysis slowly progresses, first to their hind legs, and then their forelegs, over several weeks.

But the UAB mice with the SOCS3 mutation reacted differently when given MOG.

"What we saw was unexpected," said Benveniste, the paper's senior author and chair of UAB's department of cell, developmental and integrative biology. "They twirl off-balance. They spin and flip over."

Instead of attacking neurons progressively up the spinal column as in the typical experimental disease, the damage in the UAB mice was hitting the cerebellum of the brain.

The disease was faster and harsher than the typical disease, and the mice had to be killed by day 14.

What was making such a difference?

Monday's UAB paper takes a detailed look into the interplay of cells and molecules in these mice.

One difference in the mice was a change in the balance of M1 and M2 macrophages. M1 macrophages are a type of immune cells created as part of the body's response to an invader or trauma. They act like an accelerator to boost or rev up the immune response.

M2 macrophages are the opposite -- they act like a brake to dampen the immune response.

The UAB mutant mice had an excess of M1 macrophages, making them prone to a violent autoimmune reaction when injected with the MOG. The UAB researchers found that if they injected M2 macrophages into the tail vein of these mice in an effort to "rescue the mice with the good guys," Benveniste said, the disease was much less severe.

"Overall, this tells us that SOCS3 is important," said Qin. "If mice don't have it, they get severe disease."

Now the UAB researchers are testing whether the mice with the SOCS3 mutation can serve as useful models in other neurological disease:

  • UAB is collaborating with Ohio State researchers on spinal cord injuries, because those injuries also show a profile of excess M1 macrophages.
  • UAB Parkinson's disease researchers are looking at the mice, because Parkinson's shows some of the same neuroinflammatory responses as the UAB mutant mice.
  • Benveniste and colleagues are using the mice to test some inhibitor drugs that were designed for rheumatoid arthritis.

Initial, unpublished results with the drugs are encouraging, suggesting they need to be examined for possible use in multiple sclerosis treatment.

"The data we've gotten with the inhibitors is very striking," Benveniste said.

Join the conversation by clicking to comment or email Hansen at