Tagged: blood-brain barrier
Biological systems, such as the circulatory, respiratory, and nervous systems, are groups of organs that function together to perform a common task. Some can also participate in crosstalk with other organ systems. The respiratory system, for example, brings in the oxygen that the circulatory system delivers to all the cells of the body, and maintains blood pH. The endocrine and nervous systems are signaling systems that facilitate communication between different parts of the body by use of hormones and neurotransmitters, respectively. These connections are numerous and complex, but it was previously thought that the immune system and the nervous systems were separate and largely autonomous.
In June 2010, Mauricio Vargas and colleagues from Stanford University School of Medicine reported research in Proceedings of the National Academy of Sciences showing that endogenous antibodies play an important role in repairing peripheral nervous system (PNS) damage. Antibodies are a principal part of the adaptive immune response to infection, but this research suggested that antibodies are also able to clear degenerating myelin which inhibits axon regeneration, akin to a homeostasis function. This repair was only present after PNS injury, whereas myelin debris remained in the central nervous system (CNS) white matter for years. The well known blood-brain barrier concurs with this separation in responses, as it is understood to be impermeable to large proteins such as antibodies.
Various new studies, however, have shown that behavior, mood, and memory can all be influenced by aspects of the immune system, suggesting that antibodies can somehow infiltrate the brain.
Sammy Maloney was a happy and outgoing 12-year-old boy. In 2002, however, his mother started to notice curious deviations in his personality. In six months, he underwent complete mental deterioration and was diagnosed with obsessive compulsive disorder and Tourette’s syndrome. Shortly afterwards, he was found to be harboring a streptococcal infection, although he exhibited no physical symptoms of one. Interestingly, when he started taking the prescribed antibiotics, his behavior markedly improved.
Madeline Cunningham at the University of Oklahoma has spent several years investigating various behavioral disorders associated with streptococcal infections. Cunningham has shown that antibodies against one group of streptococcal bacteria are able to bind to a site in the brain that controls movement, and consequently trigger the release of dopamine. This could explain the emotional disturbances associated with these types of disorders (1).
Studies also suggest that an activated immune system has other perceivable effects on the nervous system. For example, Jonathan Kipnis of the University of Virginia and his colleagues have shown that learning triggers a stress response in the brain, which causes CD4 cells, a type of T lymphocytes, to gather at the meninges and release interleukin-4. IL-4 switches off the stress response and causes a release of brain-derived neurotrophic factor, which facilitates memory formation. Interestingly, cancer patients treated with chemotherapy drugs often experience various cognitive defects and some memory loss. This is commonly called “chemobrain”, and these studies raise the possibility that it is a consequence of immunosuppression. Finally, an immune response against Mycobacterium vaccae has been shown to improve mood by causing neurons in the prefrontal cortex to release excess seratonin.
So it could be that the blood-brain barrier is kind of leaky after all. Understanding the connections between the immune system and the brain could lead to all sorts of ingenious treatments for various disorders. Perhaps those scientists at Stanford will utilize antibodies to develop a treatment for central nervous system repair. Perhaps we’ll one day be faced with immuno-emotive treatments for depression. Who knows? Anything is possible when a long-standing “truth” turns out not to be absolute – I’m optimistic since scientific advancement is often built on the refinement of prior knowledge.
Happiness is Catching – New Scientist
Endogenous Antibodies Promote Rapid Myelin Clearance and Effective Axon Regeneration after Nerve Injury – Proceedings of the National Academy of Sciences
Previous The Nerve Blog post About PNAS Article
(1) Antibodies raised against the Streptococcal M protein and human myocardial tissue, and Guillain-Barre syndrome in response to Campylobacter infection, are well studied examples of cross-reactivity between anti-pathogen antibodies with host tissues.
Tumors on the Brain
August 25, 2009 marked the day that America, and most importantly Massachusetts, lost one of its greatest senators, Ted Kennedy. Kennedy was diagnosed with a type of brain cancer called glioblastoma multiforme (GBM) in May 2008 after suffering from a seizure. GBM is a tumor formed in the glial, or supportive, brain cells; there is no current evidence for a genetic predisposition to this type of cancer. The American Cancer Society believes that 21,000 Americans are diagnosed with brain tumors, and about 10,000 are GBMs. They are the most aggressive and common type of brain tumor, which are resistant to many types of treatments. Only 3% of patients diagnosed with these tumors generally survive five years after diagnosis.
Almost two years after Kennedy’s death, doctors are using the drug Avastin to treat GMBs. Avastin blocks the growth of new blood vessels, a necessary component for the survival of tumors. More