What's In Your Brain?

Monday, October 24, 2005

How Jumping Genes Alter Our Wiring
Why are no two human brains alike? Medical geneticists say it could be that jumping genes rearrange our mental structure.Jumping genes, or transposons, are bits of DNA that can move freely about the genome. For unknown reasons, they either travel to a new spot or paste copies of themselves into random stretches of DNA, sometimes wreaking havoc.

Transposons are already thought to be responsible for some mutations in sperm and eggs, such as the genetic changes that cause hemophilia. But scientists had no clue that these restless genes might be active elsewhere. University of Michigan geneticist Fred Gage and his colleagues found that a transposon called LINE-1 readily moves around in the brains of mice, suggesting that the same gene may do likewise in humans. The reshuffling seems to take place starting before birth and continuing throughout life in places like the short-term memory center. According to Gage, not only do humans have a much higher proportion of transposons in their genomes than other animals but the LINE-1 seems predisposed to alter genes for brain function.

“Whether it is going to have any effects on learning, memory, and behavior, we just don’t know,” says Haig H. Kazazian Jr., who heads the genetics department of the University of Pennsylvania Medical School. But if transposons do spawn variety in mental architecture, that could help explain the differences in identical twins, says Gage. “Even though they are clones, they have their own personalities.”Jessa Forte Netting

Introducing Brains in a Bottle
Neuroscientist Gary Lynch at the University of California at Irvine says he has created a compound to make you temporarily smarter. He spent the last decade figuring out how to make brain cells more efficient at passing along signals. The result is a compound called CX717, which improves the brain’s efficiency and boosts memory power, making it a potential cure for people suffering from age-related memory loss. “It also presents a promising treatment for diseases from attention deficit disorder to Alzheimer’s—and any neuropsychiatric disorder where a breakdown in neuron communication is implicated, which is most of them,” he says.

Humans who received the drug performed better on tests assessing memory, attention, alertness, reaction time, and problem solving. Earlier studies on rhesus monkeys showed similar success. In fact, monkeys given the drug did better on tests while sleep deprived than did those who were well rested but hadn’t received it. A commercial drug is only a matter of time, Lynch says. “The days of these kinds of drugs are just beginning.”   —Jocelyn Selim

Can Tetanus Reduce Anxiety?
Like its cousin botulinum, the bacterial toxin that causes botulism, tetanus kills. When it infiltrates nerve cells, it triggers unshakable muscle contractions like lockjaw, the hallmark of tetanus. In the chest, it causes suffocation—and death. But biochemist José Aguilera of the Autonomous University of Barcelona in Spain says that tetanus—like botulinum toxin, which can tame wrinkles—has its own silver lining: as a potential new treatment for psychological disorders. Depression and anxiety are often caused by low levels of a brain chemical called serotonin, which is also crucial for regulating sleep. Because tetanus patients often suffer from insomnia, Aguilera and his colleagues reasoned that the toxin might be tinkering with serotonin levels. In animal studies, the researchers found that tetanus affects serotonin levels—but only one part of the toxin is responsible.

The tetanus toxin consists of two parts: One blocks the release from nerve cells of chemicals that stop muscles from contracting, leading to deadly spasms; the other mimics the structure of chemicals normally found in the brain, allowing the entire toxin to slip into nerve cells. It is also responsible for increasing serotonin levels.

Purified doses of the second molecule could do the same, Aguilera says, with an added benefit: The toxin (right) seems to protect nerve cells from damage, making it a possible new therapy for neurodegenerative diseases like Parkinson’s. Aguilera plans to start clinical trials in Barcelona soon using an injectable form of the toxin. If it works, treatment could be available in a few years. Kathy A. Svitil

Cerebral Chemistry Causes PMS
Neurologist István Mody of UCLA has found a biological basis for the behavior that comes with premenstrual syndrome. Visible changes in brain chemistry may underlie behavioral fluctuations, he says. During studies with mice, he concluded that female rodents were more anxious when their hormone levels mirrored those of premenstrual women. He examined the mice’s brains and found that the cells had lower levels of delta GABA, a key receptor subunit that stops nerves from firing too often and has been linked to epileptic seizures. “It’s been known for a while that epileptic women are prone to seizures around menstruation, when progesterone levels are low,” he says.

Mody hypothesizes that the seizures, irritability, and anxiety are side effects of neurons firing without inhibition. Even more intriguing, he says the regions of the brain most affected match up with those most sensitive to alcohol. Does this mean premenstrual women act as if they are intoxicated? Not really. “Although it’s acting on the same system, alcohol reduces anxiety,” Mody says. “But this does suggest there are definite changes in the brain that can play a large role in behavior.”Jocelyn Selim

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