Science Editor

Scientists are increasingly realizing that the nervous system and the immune system, once thought to be two parts of the body that were as separate as they could be while still belonging to the same organism, are intertwined in a multitude of ways.

Last week, researchers from the Wadsworth Center showed yet another connection between the two systems, demonstrating that a mouse strain with behavioral characteristics that resemble autism has immune abnormalities – in the form of high levels of antibodies and proinflammatory cytokines – as well.

Whether those high levels of immune molecules are "the main inducers" of the behavioral abnormalities still remains to be established, corresponding author David Lawrence told BioWorld Today. "Is it a consequence or a cause?"

Antibodies, he added, "may be exacerbating, but not the actual inducer."

But his team's data once again showed that "there is this intimate connection between the immune system and the nervous system."

The title of the paper, which appeared in the July 20, 2011, issue of PLoS ONE, neatly sums up its findings: "Aberrant Immune Responses in a Mouse with Behavioral Disorders."

The mice Lawrence and his team worked with are not genetically altered to lack or overexpress any one specific protein. "It's not a knockout mouse – it's just another strain of mouse," Lawrence clarified. But the strain as a whole – the BTBR strain – appears to have social problems. Mice interact less than mice from other strains, and many show repetitive behaviors, though "some are relatively normal, and others are much more extreme" in their symptoms.

Lawrence and his team originally started working with the mice to study how stress could modify the immune system.

But because of the increasing evidence for a connection between immune system abnormalities and neuropsychiatric symptoms, "we started wondering whether our mouse model would have autoantibodies."

In their current studies, Lawrence, who is chief of the laboratory of immunology at the Wadsworth Center, and his team started by testing the social behaviors of BTBR mice, which bear some resemblance to those of autistic individuals.

Modeling complex behavioral syndromes in animals, of course, has natural limits. But the team found that BTBR strain mice preferred being by themselves to spending time with a new mouse that was introduced to their cage, while mice from several other strains spent more time investigating the strangers.

The team next compared the levels of autoantibodies in BTBR mice to another strain, B6 mice, and found they were higher in both the brain and the blood of the BTBR strain. BTBR mice also had a higher proportion of helper T cells in the blood, lymph nodes and spleen.

Lawrence and his team next turned their attention to the levels of proinflammatory cytokines; neuroinflammation has been suggested as one underlying cause of autism, though the authors delicately noted in their paper that there is a "lack of consensus" about their role. Still, they found that the levels of proinflammatory cytokines interleukin-33 and interleukin-18 were higher in BTBR mice than in three other mouse strains, though the levels of interleukin-1-beta were comparable.

The work fits with other reports of a link between the two biological systems, Lawrence said.

For example, "80 percent of individuals with lupus have neuropsychiatric syndromes," though the severity of those syndromes varies "tremendously," he noted.

Furthermore, when the antibodies of lupus mice are transferred to normal mice, those normal mice come down with the same neuropsychiatric symptoms.

Neurodegenerative diseases such as Parkinson's and Alzheimer's may also have an autoimmune component, he said. (See BioWorld Today, Feb. 4, 2011.)

In their experiments, Lawrence and his team saw no sex differences in the levels of antibodies. Asked whether he found this surprising given the gender disparity in autism rates, Lawrence did not mince words: "Yes," he said. "We were anticipating that there might be a greater likelihood of seeing it in the males."

The work confirmed that BTBR mice are a good model for looking at the relationships between immune and behavioral abnormalities. For now, Lawrence and his team are looking at the animals' immune systems in more detail, looking at animals across developmental stages, and at the secretion of cytokines.