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Brain Study Finds Cell Number Rises During Childhood

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TIMES STAFF WRITER

Challenging a long-standing scientific assumption, a study of 54 human brains has found that the number of neural cells almost doubles during the first six years of life, according to researchers at UC Irvine and USC.

The new analysis, if accurate, has potential long-range implications for the treatment of brain injuries and disease, as well as more immediate import for how stimulating children may actually increase learning and cognitive ability, several other researchers said.

Some said the research, while potentially groundbreaking, would have to be scrutinized.

“The methodology here is essential, and it would have to be looked at very carefully,” said Marian Diamond, an expert at UC Berkeley on brain development.

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The analysis flies in the face of the generally accepted belief that the cerebral cortex of the human brain does not add cells during a lifetime, but rather develops by increasing the complexity of connections among existing cells.

Scientists have long known that the brain gets larger as people mature, but it is widely believed that this is because existing cells increase in size.

“What they assumed was the brain got bigger but the number of neurons stayed the same or decreased,” said Dr. William Rodman Shankle of UCI, one of the study’s authors. “The assumption was never tested.”

That is in part due to the difficulty of doing research on human brains, he said, adding that the long-standing assumptions were based on research on monkeys that is impossible to replicate in humans.

The study was published this spring in the London-based Journal of Theoretical Biology. It has caused something of a stir among neuroscientists, Shankle said, and the Society for Neuroscience has asked him to summarize it for media distribution at its annual meeting in Los Angeles in three weeks.

“I have received requests for copies of the article from some of the top neuroscientists from all over the globe,” he said from his Irvine home.

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The 25-page article was written by Shankle, a UCI professor of clinical neurology and former director of the UCI Alzheimer’s clinic; Dr. Benjamin H. Landing, an emeritus professor at USC and pediatric pathologist at Childrens Hospital in Los Angeles; and several others.

Shankle called their hypothesis revolutionary but added that further studies need to be done.

He said the idea of cell replication in the brain has met with resistance within the scientific community. Regardless of that, he said, this research demonstrates that the human cerebral cortex continues to add cells after birth.

The cerebral cortex, which contains more than half the brain’s cells, is the seat of all higher-level functions--including thought, vision, language, personality and emotion--in humans and other mammals.

“People are very excited about the possibility that the human brain can generate new neurons,” and the research opens the possibility for a wide range of medical therapies, he said.

“Let’s figure out how to make it happen in humans and how to make it happen usefully,” he said. “We could add neurons to brain areas affected by a variety of disorders from mental retardation to stroke to Alzheimer’s disease.”

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Several other scientists agreed about the possible import.

“This is the first evidence I know of a rather massive increase in cerebral cortical cells after birth,” said Dr. Arnold Scheibel, professor of neurobiology and psychiatry at UCLA School of Medicine. “It is very, very interesting, but as Shankle himself says, it needs to be repeated.”

Fred Gage, a neuroscientist at the Salk Institute for Biological Studies in La Jolla, said that in addition to the possibilities for injury and disease therapies, it is provocative to think that childhood development might be enhanced.

It has been thought, he said, that enriching a child’s environment “strengthens connections and allows the brain to make more connections,” but here the “suggestion is that there is a layer on top of that and that you can actually get more cells.”

Gage is among those who do not accept the dogma that the brain adds few, if any, cells after birth. He has done research showing that adult mice, given the proper stimulation, add brain cells and perform better in tests of agility and intelligence.

“The analysis and the uniqueness of this data set suggest that one should add this to the growing list of studies supporting tremendous [flexibility] and change in the brain,” he said.

Some find the study’s conclusions surprising.

“There is an awful lot of data out there that suggests it is not an accurate finding,” said William T. Greenough, an authority on the neurobiology of learning and memory at the University of Illinois. “That work says the division of neurons is more or less complete by the time of birth.”

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Others criticized the research because it uses derivative data to come to its conclusions rather than cell counts done by the authors.

The study relied on seminal research done by professor Jesse LeRoy Conel of Boston University 30 years ago on 54 brains of normally developing infants and children, who died from accidents not affecting the brain.

Conel collected tissue samples, created slides and drawings, and counted cells on 9 million microscopic features across more than 35 areas of the cerebral cortex, according to the paper. Conel’s work was published in eight volumes, and covers five to nine brains for each of eight age points between birth and 72 months.

Shankle, a statistician as well as a physician, was intrigued by the idea of quantitatively analyzing the Conel material. He, Landing and four others took two years to double-check and computerize the data from Conel’s published tables of cell counts. Their analysis was done from that material.

In their study, Shankle and Landing found that the growth in cell counts come in two waves, increasing by about 30% from birth to age 3 months. It then declines until age 24 months, before cell counts increase between 70% and 83% at 72 months, amounting to cells having reproduced almost double the number that existed at birth.

Even those counts were about 23% lower than values reported in other studies for humans at age 18, Shankle said. So it appears that the total number of neural cells double from birth to age 18, he said.

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The paper notes that the original Conel tissues and slides “appear to have been lost at Boston University or at Harvard Medical School,” so the cell counts made by Conel cannot be verified.

(BEGIN TEXT OF INFOBOX / INFOGRAPHIC)

Brain Power

Researchers studying the human brain have found, contrary to general scientific belief, cells in the cerebral cortex continue to reproduce at least through early childhood.

Cerebrum: Responsible for sensory and motor skills, thinking, speaking and memory

Cerebellum: Responsible for balance, coordination

Brain stem: Connects cerebrum with spinal cord

Researchers studied the cerebral cortex, the cerebrum’s wrinkled outer layer that forms the folds of the brain

Sources: Journal of Theoretical Biology, World Book Encyclopedia

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