The Principal Investigator

A recent paper from a consortium including researchers from the National Institute of Mental Health (NIMH), the Lieber Institute on Brain Development, and Johns Hopkins documents the DNA methylation pattern in the human prefrontal cortex across the lifespan. At first glance this article seems exceedingly technical and not of general interest. Now I may be biased because I study a disease (schizophrenia) with significant developmental aspects, but I believe this paper is full of incredible, novel findings on gene expression. The main points of this paper are concepts that we all should be concerned with. It gets to the crux of the age-old nature vs. nurture argument.

The study generally deals with a relatively new field of study known as epigenetics. Epigenetics deals with changes in gene expression, some potentially heritable, that do not include changes to the underlying DNA sequence. This particular article is concerned with DNA methylation. Long story short, DNA methylation leads to the silencing genes and subsequently less mRNA and protein produced by the silenced gene. More genes are silenced as we age. This makes since as development and growth, both physical and mental, should require the products of a greater number of genes. Interestingly, genes that become silenced as we age consist of many many integral players in what we consider “aging.” These include tumor suppressors and DNA repair genes.

We know that environmental experience can lead to epigenetic alterations that affect gene expression. For example, we know that maternal attention (licking, grooming, etc.) leads to epigenetic changes that facilitate anxiolytic responses in the offspring. This finding gets me to the title of this post: How much of what we now call environmental factors actually exert their effect through changes in gene expression. Potentially long-lasting changes in gene expression. I wonder how many experiences that we think are in our past, both positive and negative, that are still with us epigenetically?

The protein garbage (a.k.a. amyloid plaques) that disrupts the normal function of neurons in Alzheimer’s disease also pollutes the abundant support cells of the brain, creating a global disturbance that was previously unrecognized, according to a study in today’s (2.27.09) issue of the journal Science.

Scientists say the findings suggest plaques might have a “more complex role in altering the brain function than previously thought” and may offer new directions for treatment of what’s currently an irreversible and deadly disease.

“This study not only provides insight into the role of astrocytic networks in the brain, it also suggests new opportunities to manipulate these networks to treat or prevent Alzheimer’s disease as well as other neurological disorders,” Brian Bacskai, of Massachusetts General Institute of Neurodegenerative Disease, said in a news release. Bacskai was the senior author of the Science article.

More than 5 million Americans are living with Alzheimer’s disease – a number that is expected to grow rapidly as America’s baby boomers grow older, according to a 2008 report by the Alzheimer’s Association.

Once regarded as the wallflowers of the brain that passively support the chattering neurons as they form memories and respond to daily stimuli, in the early 90s scientists discovered astrocytes had a few tricks up their sleeves. Just like neurons communicate via electrochemical signals, the researchers found astrocytes transmit long-distance calcium signals in response to stimuli.

Previous studies have shown that the protein plaques in close proximity to neurons is a recipe for neuronal disaster, often leading neurons to die, but researchers were less sure about the effects, if any, plaques had on astrocytes.

The team of researchers used two different imaging techniques and small-molecule calcium dye to probe the astrocytes in the brains of mice genetically altered to develop Alzheimer’s plaques as they aged.

The researchers found higher resting levels of calcium in the network of astrocytes regardless of the proximity to plaque compared to normal mice. Additional imaging revealed stronger and more spontaneous astrocytic signaling in mice with plaques compared to the mutants that had not yet developed plaques and normal mice.

The team then blocked all neuronal activity to determine whether neurons adjacent to plaques were causing the global distribution of astrocytic hyperactivity and found the activity of astrocytes remained unchanged.

“We’ve only begun to scratch the surface of how plaque deposition impacts astrocytes function,” said lead author Kishore Kuchibhotla, in a news release. “One key question will be how increased astrocyte signaling impacts neuronal function, and another will be whether astrocytes activity limits or intensifies plaque deposition.”

Related links:

Alzheimer’s Plaques More Complex Than Thought (U.S. News & World Report, 2.26.09)

Research reveals some of Alzheimer’s secrets (Reuters, 2.26.09)

State’s Alzheimer’s cases to nearly double by 2030 (The San Diego Union Tribune, 2.26.09)

It goes without saying that men and women don’t always see eye-to-eye, but researchers now have evidence that there’s a difference in the ways that male and female brains judge beauty.

The authors of the study, published Monday (2.23.09) in the Proceedings of the National Academy of Science (PNAS), theorize that this gender difference developed after the evolutionary split between humans and chimpanzees, roughly 4 million years ago.

The team of scientists from Spain used a technique called magnetoencephalography (MGE) to measure brain activity while men and women evaluated the beauty of 400 photographs of paintings from various artistic periods (abstract, classic, impressionist, postimpressionist), landscapes, urban areas and artifacts. The researchers deliberately excluded photographs with close up views of humans or well-known paintings so as to not distort the analysis.

During the test, the participants were asked to indicate a judgment of ‘beautiful’ or ‘not-beautiful’ for each image with a finger point. Later, the same participants ranked the beauty of the images they saw during the test.

The researchers focused their attention on the parietal lobe, a region of the brain well recognized for its role in pulling together and processing sensory information, such as sights, smells and sounds.

For the first 300 milliseconds the test, neither the brains of women or men differed in response to a beautiful versus non-beautiful image. However, after 300 milliseconds, the brain’s response to beauty became clear, with male brains displaying higher activity in the right parietal lobe in response to beautiful images. Like men, the women’s brains showed heightened activity when observing a beautiful image, but this activity appeared in both left and right sides of the brain.

Previous studies of the parietal lobe suggest the right parietal lobe is involved in the processing of coordinate spatial relationships (the distance among objects) while the left lobe assists with the processing of categorical spatial relationships (whether one object is above or below another). The authors suggest that the bilateral parietal lobe activity in women suggests they draw upon categorical information to assess beauty while men use coordinate information.

The researchers speculate that the evolution of the gender differences in response to beauty may have been born out of the exploration techniques of males and females in hunter-gatherer groups. “Tracking animals and foraging for plant food involve different spatial scenarios, and hence, require different kinds of spatial skills,” they write.