The Ballooning Brain: Defective Genes May Explain Uncontrolled Brain Growth in Autism

[Ian David]

The Ballooning Brain: Defective Genes May Explain Uncontrolled Brain Growth in Autism

Autistic children's brains may grow too big, too soon. A new study links this unusual growth to abnormal gene activity that fails to prune unnecessary neural connections

As a baby grows inside the womb, its brain does not simply expand like a dehydrated sponge dropped in water. Early brain development is an elaborate procession. Every minute some 250,000 neurons bloom, squirming past one another like so many schoolchildren rushing to their seats at the sound of the bell. Each neuron grows a long root at one end and a crown of branches at the other, linking itself to fellow cells near and far. By the end of the second trimester, neurons in the baby's brain have formed trillions of connections, many of which will not survive into adulthood—the least traveled paths will eventually wither.

Sometimes, the developing brain blunders, resulting in "neuro-developmental disorders," such as autism. But exactly why or how early cellular mistakes cause autism has eluded medical science. Now, Eric Courchesne of the University of California, San Diego, thinks he has linked atypical gene activity to excessive growth in the autistic brain. With the new data, he has started to trace a cascade of genetic and cellular changes that he thinks define autism. Although intrigued by Courchesne's work, other researchers caution that explosive neural growth is not necessarily a defining feature of all autistic brains.

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Now, Courchesne and his colleagues have analyzed DNA and RNA in 33 cubes of brain tissue from people who passed away, 15 of whom were autistic (nine children and six adults) and 18 who had typical brains (seven children and 11 adults). Looking at the order of DNA's building blocks reveals whether individual genes have mutations; measuring levels of RNA indicates how often those genes were translated into proteins. Such gene expression, Courchesne and his colleagues found, varied between autistic and typical brains. In brain tissue from both autistic children and autistic adults, genes coding for proteins that identify and repair mistakes in DNA were expressed at unusually low levels. Additionally, all autistic brains demonstrated unusual activity levels for genes that determine when neurons grow and die and how newborn neurons migrate during early development. Some genes involved in immune responses, cell-to-cell communication and tissue repair, however, were expressed at unusual levels in adult autistic brains, but not in autistic children's brains. The results appear in the March 22 issue of PLoS Genetics.

By combining his new findings with his earlier discoveries, Courchesne has started to construct a kind of timeline of autism in the brain. Perhaps, as the brain of a future autistic child develops in the womb, something—an inherited mutation or an environmental factor like a virus, toxin or hormone—muffles the expression of genes coding for proteins that usually fix mistakes in sequences of DNA. Errors accumulate. The genetic systems controlling the growth of new neurons go haywire, and brain cells divide much more frequently than usual, accounting for the excess neurons found in the PFC of autistic children. Between birth and age five, the extra neurons in the autistic brain grow physically larger and form more connections than in a typical child's brain. Unused connections are not pruned away as they should be. Later, in adolescence and adulthood, the immune system reacts against the brain's overzealous growth, which might explain the unusual levels of immune genes Courchesne found in his new study and why, in earlier work, he had discovered that when autistic children become teenagers, some brain regions actually start shrinking compared with typical brains.

More:
http://www.scientificamerican.com/article.cfm?id=courchesne-gene-expression

[KamaAina]

1. I prefer to think of neurotypicals as having a neuron deficiency

especially Teabagger types.

[Ian David]

2. One day we will all welcome our large-brained Autistic overlords. n/t

[Odin2005]

3. People always said my noggin was huge! They were right!