“Branching” Protein a Target for New Brain Drugs

The discovery of a protein’s role in regulating brain cell “branching” could lead to new treatments for memory and learning disabilities.

American researchers from Rutgers University in New Jersey have discovered that the protein, cypin, could be a new target for drugs that treat brain disorders including Alzheimer’s and fetal alcohol syndrome.

Neuron branching, more formally known as dendrite growth, is an important process in normal brain function and is thought to increase as people learn and decrease with some neurological diseases.

“The identification of cypin and understanding how it works in the brain is particularly exciting since it opens up new avenues for the treatment of serious neurological disorders,” says researcher Bonnie Firestein. “This paves the way to designing new drugs that could target this protein molecule.”

Cell shaping

Firestein first identified and isolated cypin in 1999 during her postdoctoral research.

She is now focusing on how it works in the hippocampus, a structure in the brain associated with the regulation of emotions and memory

“We knew that cypin existed elsewhere in the body where it performs other functions, but no one knew why it was present in the brain,” she says.

Firestein and colleagues have now determined that cypin in the brain works as an enzyme that helps shape neuron “trees.”

“One end of a neuron looks like a tree and, in the hippocampus, cypin controls the growth of its branches,” Firestein explains. “An increase in the number of branches provides additional sites where a neuron can receive information that it can pass along, enhancing communication.”

Stimulated growth

The researchers found that stimulating neurons caused an increase in cypin and dendrite growth.

They also found that reducing the expression of cypin and caused a decrease in branching.

They think that cypin acts as glue that cements other molecules together into long chain structures that extend through the branches of a dendrite.

“Cypin works on tubulin, a protein that is a structural building block of the dendrite skeleton,” says Firestein. “If you just take our purified protein and mix it with tubulin in a test tube, the cypin on its own will actually cause these skeletal structures to grow.”

Back Pain Could Be Pain In Butt

Pain Could Be Caused By Misalignment Of Tailbone

Sprained muscles and ligaments, arthritis, osteoporosis and herniated discs can all cause back pain. Doctors have a lot of ways to treat back pain, including medications, physical therapy, chiropractic manipulation, injections and surgery.

Sometimes these treatments work, sometimes they don’t. And sometimes, back pain is really a pain in the butt!

Jenna Bolden has had back pain for seven years.

“It’s like knitting needles stabbing in the back,” she said.
The pain started when she was pregnant, and continued after she gave birth.
Turns out, the pain was caused by a condition known as coccydynia.
“The part or the spine involved is the very, very tip of the tailbone called the coccyx, [which is a] little bone at the bottom,” said Dr. Richard Gotlin.

The tailbone is supposed to line up with the pelvis. But it bends forward when you sit down on a hard surface.
Gotlin says coccydynia is the most common cause of back pain related to childbirth. So why have most people never heard of it?

“The most common reason we don’t see this often is because of misdiagnosis or under diagnosis, like many things in medicine we haven’t discovered it or we don’t know about it,” he said.
So most doctors assume it’s typical back pain and prescribe treatments like anti-inflammatory medications and physical therapy.

However, Gotlin suggests a different kind of therapy. He says the treatment for coccydynia is to put the tailbone back in the right place. Gotlin does that by going through the rectum and pulling the tailbone back. That relieves the pain.

It doesn’t sound pleasant, but, Holden says it works.
“Once you have been through it two or three times it’s not uncomfortable at all,” she said. “[The procedure] gets that tailbone and puts it into place and it’s like immediate relief.”
Gotlin says the procedure works with about 60 to 80 percent of the patients he treats.

Search for Alcoholism Genes Narrowed

Bringing them closer to identifying genetic contributors to alcoholism, researchers have identified three chromosome locations that hold genes related to the risk of becoming an alcoholic.

Their study, published in this month’s issue of Alcoholism: Clinical & Experimental Research, identifies three chromosomal regions in the human genome that hold genes related to a low response to alcohol, which has been linked to alcoholism in later life.

“The research doesn’t tell us how many genes are involved, or how the genes work to cause this effect,” says Kirk Wilhelmsen, principal investigator at the Ernest Gallo Clinic and Research Center and the study’s first author.

But the study is a major step towards identifying genes that confer risk for alcoholism or allow alcoholism to develop.

Good to not hold your liquor

Twenty-five years ago, response to alcohol was measured in young nonalcoholic college students.

Many years later, the young men who exhibited a low response to alcohol were more likely to become alcoholics.

It is now known that those who are easily intoxicated by small amounts of alcohol at an early age are less likely to become alcoholics while those who require more drinks to be affected have a greater risk.

Identifying chromosomes

For their study, Wilhelmsen and colleagues used students attending two San Diego universities. Each student in the study was between the ages of 18 and 29, had an alcoholic-dependant parent, a personal history of drinking but no dependence on alcohol and a full sibling with similar characteristics.

Both the full siblings and the parents were genotyped for 811 satellite markers. They were then given eight minutes to consume a beverage that had its alcoholic taste and quantity disguised.

Subjects were measured at 15 minutes, 30 minutes and every 30 minutes after that in a three-hour session that gauged body sway and positive and negative feelings.

“We found that there were three locations that had the largest evidence for genes that affect the level of response to alcohol,” says Wilhelmsen.

The locations are on chromosomes 10, 11 and 22.

Pinpointing variations

Identification of chromosome locations that may affect someone’s risk for becoming an alcoholic is important because it “may lead to the identification of specific genes that determine how alcohol makes us feel, gives us new insight into how the brain works and help us understand why some people become addicted to alcohol,” says Ivan Diamond, professor and vice-chairman of the department of neurology at the University of California, San Francisco.

The researchers will now investigate individual variations of genes further.

They hope that genes with known actions from the 200 to 300 in each identified chromosome region will prove to play a role, but it’s possible that the regions contain genes about which little is known, which will make their work more difficult.

Stem-like Cells from Blood Show Promise for Stroke

Intravenous injections of stem-like cells obtained from circulating human blood have helped rats recover from a severe stroke, suggesting a new cell therapy for human stroke victims.

Reporting in the journal Cell Transplantation, researchers from the University of South Florida Center of Excellence for Aging and Brain Repair describe injecting human blood donors with a compound called granulocyte stimulating factor to stimulate the release from bone marrow of stem-like-cells known as peripheral blood progenitor cells.

The stem-like cells are easy to extract and able to promote faster recovery from chemotherapy, making them already an alternative to bone marrow transplants for patients with blood cancers.

“This is the first demonstration that G-CSF stimulated peripheral blood cells promote recovery after a stroke,” says Alison Willing, assistant professor of neurosurgery and first author of the study.

Back to normal — almost

For the study, Willing and colleagues compared the effect of G-CSF stimulated peripheral blood cells with that of human umbilical cord blood cells, which studies suggest help rats recover from stroke.

Three groups of rats were induced to have symptoms of stroke. The research team then injected the first group with G-CSF stimulated peripheral blood cells — collected from the blood of human donors — 24 hours after a stroke.

The second group was injected with umbilical cells 24 hours after a stroke.

The third group received no cellular treatment.

“Pretty amazing”

Researchers found that both cell therapies reduced stroke-induced hyperactive behavior back to pre-stroke levels. Also, the therapies prevented the rats from developing stroke associated motor asymmetry — the favoring of one side over another.

“We were putting these cells into animal 24 hours after a stroke and seeing significant behavioral improvement,” she says. “The animals behaved almost normally on our tests, just as they had before the stroke. That’s pretty amazing.”

Researchers suspect that the transplanted cells secrete a protective substance that prevents further brain damage in stroke victims, rather than replacing damaged brain cells. But more research is needed to determine how the cells work.

For human treatments, patients might be able to use their own peripheral blood cells as a source of cell therapy for stroke, avoiding problems of immune rejection.