Can the developing brain of a fetus be adversely affected when its mother is suffering from a virus or infection? The long-held theory believed by developmental neurobiologists and researchers was that the nervous and immune systems are completely separate. The blood vessels and capillaries in the brain are protected by the blood brain barrier, which is an area surrounding the brain that prevents the entrance of foreign substances. So, the blood brain barrier should prevent immune molecules from entering and disturbing brain development in a fetus. However, groundbreaking research has proved that is not the case.
Dr. Kim McAllister, associate professor of neurobiology, physiology and behavior and a member of the Center for Neuroscience at UC Davis, is currently studying the presence of immune system molecules in neurons. “About 10 years ago, researchers at Stanford University found that immune system proteins known as major histocompatibility complex (MHC) proteins are present in the brain,” explained Dr. McAllister.
In other words, the theory that the nervous system is separate from the immune system has been proved wrong. This implies that immune responses during pregnancy result in increased amounts of immune system molecules in the baby’s developing brain. This may be a precursor to developmental and degenerative disorders.
Dr. McAllister’s lab has been observing exactly how the presence of these proteins affects brain development. “We are looking at how MHC proteins affect synapse formation during development. We have found that the MHC molecules are present during initial formation of cerebral connections,” she said. Her lab has also manipulated levels of MHC molecules to determine how an increased amount may alter connections. Sure enough, increasing amounts of MHC immune proteins altered brain development and resulted in decreased amounts of neuronal synaptic connections.
Another exciting aspect of this discovery is that MHC proteins are the first molecules that negatively regulate formation of synaptic connections in the brain. “Most molecules present in the developing cerebral cortex promote the growth and formation of synapses. MHC proteins cause elimination of synapses, which says that formation of these connections might actually result from a push-pull system of opposing molecules.”
Dr. McAllister’s lab has recently been collaborating with Cal Tech to determine the effect that injecting a virus into pregnant mice has on offspring. “Injecting the virus into pregnant moms causes them to become sick and lose weight. They then recover and give birth. We compared behavior in offspring of mothers who had been given the virus versus offspring of mothers who had been given control injections. Only the offspring of the moms who received the virus expressed aberrant behavior,” stated Dr. McAllister. This provides further evidence that immune response reaches and affects development of the brain, which can result in behavioral differences later in life.
This research has not only proved that strong immune responses during pregnancy can lead to disorders such as autism and schizophrenia, but will also help scientists understand how these immune response mediated diseases can be prevented. This has been the first step to unravelling the mystery of severe neurodegenerative disorders and has completely changed the scientific perspective of the immune system.