Monday, January 18, 2010

The female brain

"Ah! The strength of women comes from the fact that psychology cannot explain us. Men can be analysed, women merely adored," says a character in Oscar Wilde’s play, "An Ideal Husband." Would you believe that, despite the advances on issues about gender equality, the female brains are still wired for Stone Age necessities? This is a fascinating fact for feminists, and for men who cannot understand women. It may explain, in part, why a woman is an enigma.
Research shows that male and female brains are very different -- in architecture and chemical composition. Dr. Louann Brizendine, neuropsychiatrist at UCSF, asserts, "The sooner women -- and those who love them -- accept and appreciate how those neurological differences shape female behavior, the better we can all get along."

It almost impossible to show why and how women and men are so different.

One way to describe the contrasts is to use metaphors of women on highways and men on country roads to illustrate emotions.

"Women have an eight-lane superhighway for processing emotion while men have a small country road. Men have O’Hare airport as a hub for processing thoughts about sex, where women have an airfield nearby that lands small and private planes," Dr. Brizendine explains. Sex thoughts for men are like extremely busy airports while women use small planes on obscure landing fields.

The studies were based on comprehensive scientific studies from genetics, molecular neuroscience, fetal and pediatric endocrinology, and neurohormonal development. They do not necessarily reflect the workings of the Asian male and female brains. (That would probably be more complex and need voluminous cultural data.)

Here are a few significant neurological differences on "head cases."

1. Women remember fights that a man insists never happened.

2. Women excel at knowing what people are feeling. Men have difficulty spotting an emotion unless someone cries or threatens bodily harm.

3. Women over 50 are likely to initiate divorce. (In the local setting, women choose to stay in the marriage for practical reasons -- social status and family pressure, financial dependence.)

4. Women use 20,000 words per day. Men use only 7,000 words per day.

5. Thoughts about sex enter women’s brains once every couple of days. For men, thoughts about sex occur every minute.

Dr. Brizendine’s interesting insights show the following:

1. A financially independent woman may discuss her thoughts on finding a soul mate. However, when she meets a potential mate, her brain subconsciously sizes up his portfolio. It is the primal instinct to seek a qualified provider and protector for the family. This is the phenomenon that traces its roots to the Stone Age when women chose a mate based on his strength and ability to hunt for food. Millions of years later, the modern woman still retains that prehistoric imprint in her brain.

2. Working moms suffer withdrawal pains when they return to their jobs after giving birth. This is because they get a hormonal high from breastfeeding their babies. Thus, there is a strong reluctance to let go of the baby who depends on her. It is not merely a mood swing or the blues.

3. There is no "unisex" brain.

Girls are wired as girls, and boys are wired as boys -- from birth. The male brain may be larger overall, but the main hub for emotion and memory is larger in a woman’s brain. Her "neurological reality" is affected by the fluctuating hormonal surges throughout a woman’s life. Their brains drive their impulses values and reality.

Bruce McEwen, a Rockefeller University brain researcher wrote, "Men and women approach the same problems in somewhat different ways, at least in part because of the biological differences in the brain, which in turn interact with experience -- the nature-nurture story."

Men are from Mars. Women are from Venus, the 1993 bestseller on the culture of the brains, has made people more aware of the biological and psychological differences. This is not to say that one gender is superior to the other. There is no competition. We should celebrate the differences. It makes life so much more interesting and complex.

Scientists, however, note that there are some clear advantages of the female brain. Take the "mommy brain." This is the brain that multitasks, juggles work responsibilities and domestic chores, and tries to balance career and family.

Previous studies have shown that a woman has a "diffused consciousness" and a peripheral awareness, like a lamp that lights up a room. Men tend to focus like a spotlight on a specific area.

Dr. Brizendine studied neurobiology at UC Berkley in the 1970s. She discovered during that period that manipulating the hormones of an animal produced different behaviors.

It was the era and culture of domesticity that prevented many women from achieving their full potential. Emancipation happened some 20 years later.

At Yale Medical School, Dr. Brizendine was astounded that studies on the brain were exclusively based on males. Research did not include females because, as her professor said, "The menstrual cycles would mess up the data."

(The chauvinist male can provoke major discussions with an emancipated feminist. In the ’70s, modern women were asserting themselves in fields such as science and medicine, traditionally dominated by men.)

She did not argue with her professor. However, she wanted to ask him, "Then how can you make medications, and how can you make assessments that you’ll apply to female patients when you don’t really know?å

It was a valid point and one that she eventually pursued when she established the Women’s and Teen Girls’ Mood and Hormone Clinic at UCSF in 1994. It is the only psychiatric facility in the US with such a comprehensive focus. (A satellite clinic at SF General Hospital has a center for cultural issues and concerns of African American Women, Latinas, and lesbians.)

Dr. Brizendine has one important point for all women and those who love them.

The female brain naturally releases oxytocin after a 20-second hug. The embrace bonds the huggers and triggers the brain’s trust circuits.

She advises, "Don’t let a guy hug you unless you plan to trust him, and if you do, make sure it last 20 seconds."

Cancer Stem Cells Suppress Immune Response Against Brain Tumor

Article Date: 17 Jan 2010 - 0:00 PST

Cancer-initiating cells that launch glioblastoma multiforme, the most lethal type of brain tumor, also suppress an immune system attack on the disease, scientists from The University of Texas M. D. Anderson Cancer Center report in a paper featured on the cover of the Jan. 15 issue of Clinical Cancer Research.

The researchers demonstrate that this subset of tumor cells, also known as cancer stem cells, stifles the immune response in a variety of ways, but that the effect can be greatly diminished by encouraging the stem cells to differentiate into other types of brain cell.

"We've known for years that glioblastoma and cancer patients in general have impaired immune responses," said senior author Amy Heimberger, M.D., an associate professor in M. D. Anderson's Department of Neurosurgery. "Our research uncovers an important mechanism that shows how that happens. The cancer stem cells inhibit T cell response, and it is these T cells that recognize and eradicate cancer."

Definitions of cancer stem cells vary. To meet the researchers' definition, the cells had to express a marker called CD133, form neurospheres (little round balls) in culture, and be able to recreate glioblastoma multiforme when injected into the brain of a mouse. They also had to be capable of differentiating into specific types of brain cells - neurons, astrocytes and glial cells.

Glioblastoma stem cells have been implicated in tumor resistance to chemotherapy and radiation, and are the believed to be responsible for the relentless recurrence of the disease, said first author Jun Wei, Ph.D., an instructor in the Department of Neurosurgery.

Wei explained that the glioblastoma stem cells suppress T cell response three different ways by:

- Producing immunosuppressive cytokines that prevent the responses of T cells.
- Inducing some T cells to become regulatory T cells, which act as brakes on the immune response.
- Killing T cells via apoptosis, or programmed cell suicide. This is accomplished via the immunosuppressive protein B7-H1 in the stem cells directly contacting the T cells or by secretion of Galectin-3.

Wei said this immunosuppressive effect was reversed when the team placed the undifferentiated glioma stem cells in a culture medium that causes them to differentiate into the three types of neural cell.

"There are multiple research groups around the country, including ours, trying to develop vaccines or other immunotherapeutics against glioma stem cells," Heimberger said. "Now we have to be cognizant that the stem cell may deliver a fatal blow back to the immune system, which will help us understand how to design immune-based therapies."

New drugs or combination therapies are needed, because after decades of research, little progress has been made in treating glioblastoma multiforme. With the best of care patients survive an average of 14 months.

STAT3 pathway inhibits T cell response

In a separate paper in the Jan. 15 issue of Molecular Cancer Therapeutics, the research team also reports that the STAT3 signaling pathway is highly active in glioblastoma stem cells and suppresses immune system response.

Heimberger said the STAT3 molecule is known to induce cancer proliferation and survival migration and invasion, growth of new blood vessels, and immunosuppression.

Inhibiting STAT3, either by silencing it with small interfering RNA or by treatment with an experimental drug called WP1066, reactivates the immune response.

"We showed that if you treat the cancer stem cells with an inhibitor of STAT3, you can restore T cell proliferation and the ability of those cells to make pro-inflammatory cytokines," Heimberger said.

While the response is powerful it is not complete, so the researchers conclude there a STAT3-independent pathway is also at work in mediating immune suppression.

Research continues on how the inhibitors work, and whether they cause the stem cell differentiation that the team has shown reverses immune suppression.

The experimental drug WP1066 was developed by Waldemar Priebe, Ph.D., professor in M. D. Anderson's Department of Experimental Therapeutics. The drug has been shown to inhibit STAT3 in mice and reverse the immune suppression caused by cancer stem cells.

The research was funded by grants from the Anthony Bullock III Foundation, the Dr. Marnie Rose Foundation, M. D. Anderson and the National Cancer Institute.

Co-authors with Heimberger and Wei on both papers are Jason Barr, Ling-Yuan Kong, Ph.D.,Yongtao Wang, Adam Wu, M.D., Amit K. Sharma, Joy Gumin, Verlene Henry, Raymond Sawaya, M.D., and Frederick Lang, M.D., all of the Department of Neurosurgery; and Howard Colman, M.D., Ph.D., of M. D. Anderson's Department of Neuro-Oncology. Priebe is a co-author on the STAT3 paper.

The University of Texas M. D. Anderson Cancer Center