August 29, 2008

Aliquots — Research highlights from VUMC laboratories

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We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to:

Keeping brain fit after radiation

Radiation therapy to the head is essential for treating brain tumors and brain metastases. But the treatment often damages the hippocampus – the brain’s short-term memory center – and leaves the patient with long-term learning and memory impairments.

In the July issue of Cancer Research, Dinesh Thotala, Ph.D., Dennis Hallahan, M.D., and Eugenia Yazlovitskaya, Ph.D., identified a protein, GSK-3beta, that plays a key role in radiation-induced hippocampal damage and contributes to this cognitive decline. They found that inhibiting GSK-3beta activity with small molecules or by genetic manipulation prior to irradiation prevented the death of cultured hippocampal neurons. The small molecule inhibitors also protected hippocampal neurons and improved learning and memory in mice treated with radiation.

The results suggest GSK-3beta inhibitors may have a therapeutic role in protecting the brain and limiting cognitive impairments associated with radiation treatment, improving the quality of life in cancer survivors.

To see the study, go <a href="">here</a>.

— Melissa Marino

A pain in the baroreceptor

Elevated blood pressure has been linked to reduced pain sensitivity. Artificially stimulating the body’s baroreceptors – proteins that sense and help maintain blood pressure – reduces pain, but the role of a person’s natural baroreceptor reflex sensitivity (BRS) in pain relief remains unclear.

Ok Yung Chung, M.D., M.B.A., and colleagues investigated the link between BRS and acute pain responses in healthy, pain-free subjects and individuals with chronic low back pain. In the Aug. 15 issue of Pain, they report a significant inverse association between BRS and acute pain responses in pain-free individuals. However, patients with chronic low back pain showed lower resting BRS than healthy subjects, but no significant relationship between BRS and pain responses, suggesting altered baroreceptor function in this group. BRS-related pain relief, they found, is partially mediated by the alpha2-adrenergic receptor signaling pathway, and blocking this pathway could normalize baroreceptor function in individuals with chronic pain.

The results provide insight into pain control mechanisms and the relationship between hypertension and chronic pain.

To see the study, go <a href="">here</a>.

— Melissa Marino

Life-death balance in the colon

Maintaining the intestinal epithelium – the single layer of cells that lines the intestines and is replaced every three to five days – requires a delicate balance of cell growth (proliferation) and death. Identifying the cellular factors responsible for maintaining this balance is crucial to understanding – and developing treatments for – inflammatory bowel diseases and colon cancer.

Brent Polk, M.D., and colleagues investigated the role of Raf, an enzyme involved in cell proliferation and survival, in mice with chemically-induced colitis, an inflammation of the colon. In the August issue of Gastroenterology, they show that mice lacking Raf in their intestinal epithelium develop worse colitis – exhibiting increased cell death and decreased cell proliferation – in the intestinal epithelium than normal mice. Additionally, they identified two different pathways through which Raf likely works to aid recovery of the intestinal epithelium.

Based on the demonstrated protective role for Raf, the researchers are now investigating the effects of Raf-targeted therapies in animal models of inflammatory bowel disease and colon cancer.

To see the study, go <a href="">here</a>.

— Melissa Marino

Stem cells have a change of heart

Pluripotent stem cells, which can “mature” into multiple tissue types, show promise as a versatile source of cells for regenerating damaged adult tissues such as heart muscle. But first, investigators must develop reliable tools and methods for coaxing them to become desired cell types.

Charles Hong, M.D., Ph.D., Antonis Hatzopoulos, Ph.D., and colleagues examined the effects of dorsomorphin, a small molecule inhibitor of bone morphogenetic protein (BMP) signaling, on mouse embryonic stem (ES) cells. They report in the August PLoS ONE that dorsomorphin – like the natural BMP inhibitor Noggin – induces the development of spontaneously beating heart muscle cells. Dorsomorphin treatment limited to the first 24 hours of ES cell differentiation was effective, in contrast to Noggin, which requires five days of treatment. Dorsomorphin also reduced differentiation of the ES cells into endothelial, smooth muscle and blood-forming cells. The findings suggest that small molecules like dorsomorphin could prove valuable for translating stem cell advances into regenerative therapies.

To see the study, go <a href="">here</a>.

— Leigh MacMillan

Past Aliquots

June 22, 2012
June 8, 2012
May 11, 2012
April 27, 2012
April 13, 2012
March 30, 2012
March 16, 2012