Left Brain Damage May Make People More Vulnerable To Infection

This goes to support the belief that autism is an immune disorder.

Epilepsy surgery on brain hemispheres produces different effects onimmune system A major immunological difference between the opposite halvesof the human brain is now confirmed in a study published May 24, 2004 inthe online edition of the Annals of Neurology. Researchers have found thatdamage or surgery to the left half of the brain may make a right-handedperson more susceptible to being immunocompromised. The results might help to explain intriguing earlier findings thatsuggested people who had strokes on the left side of their brains were moresusceptible to infections.

“These findings raise the possibility that doctors need to be moreaggressive in protecting patients from infection following strokes orsurgery on the left side of the brain,” said study director Kimford J.Meador, MD, of Georgetown University Hospital in Washington, D.C.

Are you a right-brain person–creative, emotional, big picture–or aleft-brain person–logical, detail-oriented, practical? The idea that thetwo halves of our brains are fundamentally different has settled comfortably in our imaginations, thanks equally to science fiction andself-help books. But beyond a predominant role in language for the lefthalf, scientists have had a hard time pinning down what these differencesmean for how our brain works. Animal studies have shown distinct differences in how the two brainhalves are linked to the immune system. Several years ago, Meador and his colleagues found preliminary evidence of similar differences in humans,which could be of great significance for medicine.

“The immune and nervous systems are interlinked, influencing eachother in complex ways that we are just beginning to understand,” saidMeador. In the present study, the researchers examined how the immune systemresponded to surgery on either side of the brain, following the progress of22 epilepsy patients who had parts of their brain surgically removed in anattempt to control debilitating seizures. Most patients who had surgery on the left side of their brains experienced significant decreases in immune function, with the immunesystem reducing the numbers of critical disease-fighting cells calledlymphocytes and T-cells.

By contrast, patients who had surgery on the rightside of their brains saw the levels of their lymphocytes and T-cellssignificantly boosted. It is important to note that this may be true only for right-handedpatients, write the authors. Although they did not have enough left-handedand ambidextrous people in their study, the researchers note thatnon-right-handed people could have the opposite reaction. Or they mightshow equivalent immunologic responses to right and left brain injuries.

“Even with these results, we and others have examined only a smallportion of possible immune responses in regards to left/right braininfluences. Even more important, exactly how the brain alters immuneresponse is unclear. Future studies will need to address these issues,”said Meador.

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The Arg451Cys-neuroligin-3 Mutation Associated With Autism Reveals A DefectIn Protein Processing.Comoletti D, De Jaco A, Jennings LL, Flynn RE, Gaietta G, Tsigelny I,Ellisman MH, Taylor P. Department of Pharmacology, University ofCalifornia, San Diego, La Jolla, California 92093-0636, USA. The neuroligins are a family of postsynaptic transmembrane proteinsthat associate with presynaptic partners, the beta-neurexins. Neurexins and neuroligins play a critical role in initiatingformation and differentiation of synaptic junctions. A recent study reported that a mutation of neuroligin-3 (NL3), anX-linked gene, was found in siblings with autistic spectrum disorder inwhich two affected brothers had a point mutation that substituted a Cys forArg451. To characterize the mutation at the biochemical level, we analyzedexpression and activity of the mutated protein.

Mass spectrometry comparison of the disulfide bonding pattern betweenthe native and the mutated proteins indicates the absence of aberrantdisulfide bonding, suggesting that the secondary structure of the mutatedprotein is conserved. However, the mutation separately affects protein expression andactivity. The Cys mutation causes defective neuroligin trafficking, leading toretention of the protein in the endoplasmic reticulum. This, in turn, decreases the delivery of NL3 to the cell surface.

Also, the small fraction of protein that reaches the cell membranelacks or has markedly diminished beta-neurexin-1 (NX1beta) binding activity. Other substitutions for Arg451 allow for normal cellular expressionbut diminished affinity for NX1beta. Our findings reveal a cellular phenotype and loss of function for acongenital mutation associated with autistic spectrum disorders. PMID: 15152050 [PubMed – in process]

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