In a further test of a novel theory that suggests autism is the consequence of abnormal cell communication, researchers at the University of California, San Diego School of Medicine report that an almost century-old drug approved for treating sleeping sickness also restores normal cellular signaling in a mouse model of autism, reversing symptoms of the neurological disorder in animals that were the human biological age equivalent of 30 years old.
The findings, published in the June 17, 2014 online issue of Translational Psychiatry, follow up on similar research published last year by senior author Robert K. Naviaux, MD, PhD, professor of medicine, pediatrics and pathology, and colleagues.
Naviaux said the findings fit neatly with the idea that autism is caused by a multitude of interconnected factors: “Twenty percent of the known factors associated with autism are genetic, but most are not. It’s wrong to think of genes and the environment as separate and independent factors. Genes and environmental factors interact. The net result of this interaction is metabolism.”
Naviaux, who is co-director of the Mitochondrial and Metabolic Disease Center at UC San Diego, said one of the universal symptoms of autism is metabolic disturbances. “Cells have a halo of metabolites (small molecules involved in metabolism, the set of chemical processes that maintain life) and nucleotides surrounding them. These create a sort of chemical glow that broadcasts the state of health of the cell.”
Cells threatened or damaged by microbes, such as viruses or bacteria, or by physical forces or by chemicals, such as pollutants, react defensively, a part of the normal immune response, Naviaux said. Their membranes stiffen. Internal metabolic processes are altered, most notably mitochondria — the cells’ critical “power plants.” And communications between cells are dramatically reduced. This is the “cell danger response,” said Naviaux, and if it persists, the result can be lasting, diverse impairment. If it occurs during childhood, for example, neurodevelopment is delayed.
“Cells behave like countries at war,” said Naviaux. “When a threat begins, they harden their borders. They don’t trust their neighbors. But without constant communication with the outside, cells begin to function differently. In the case of neurons, it might be by making fewer or too many connections. One way to look at this related to autism is this: When cells stop talking to each other, children stop talking.”
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