November 16, 2007

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:

Volume control key to nerve survival

Peripheral neuropathy and mental retardation are hallmarks of the rare neurological disorder ACCPN. The disorder has been linked to mutations in the gene for the potassium-chloride cotransporter KCC3, a protein that participates in regulating cell volume.

Eric Delpire, Ph.D., Nellie Byun, Ph.D., and colleagues previously reported KCC3 knockout mice as a model for ACCPN. To explore how disruption of KCC3 leads to peripheral nerve degeneration, the investigators analyzed sciatic nerve structures in knockout and wild-type mice. In the October Neurobiology of Disease, they report that three days after birth, myelin development in the KCC3 knockout mice appeared normal, but sciatic nerve axons were swollen. As the mice aged, fluid accumulated around axons, axons and myelin degenerated, and nerve conduction decreased.

The findings suggest that cell volume regulation is critical for peripheral nerve cell maintenance, which could have implications for treating the symptoms of ACCPN and other neurodegenerative disorders.

— Leigh MacMillan

Short frogs offer ‘Wnt’ hints

The “Wnt” signaling pathway coordinates the formation of tissues, organs and limbs during development, and its misregulation later in life can lead to disease states as diverse as Alzheimer's and cancer.

As part of their efforts to understand the mechanism of Wnt signaling, Ethan Lee, M.D., Ph.D., and colleagues have studied the role of Lrp6, a co-receptor for Wnt, in Xenopus (frog) embryos. They report in the Nov. 15 Development that Lrp6 is an essential regulator of “convergent extension,” the process of cell migration and shape-changing that lengthens the embryo during development. Frog embryos with low levels of Lrp6 failed to fully elongate.

The dogma in the Wnt field is that Lrp6 participates exclusively in Wnt/beta-catenin signaling — the “canonical” Wnt pathway — but the current studies demonstrate that Lrp6 also inhibits the “non-canonical” Wnt/planar cell polarity pathway. The investigators propose that Lrp6 activity may be critical for switching between the two Wnt signaling pathways.

— Leigh MacMillan

Beware of mom’s immune system

Being born in the winter or spring — the height of cold and flu season — increases one's risk of schizophrenia and autism. While the mechanism at work is not clear, the maternal immune response stimulated by these infections is thought to influence the developing fetal brain.

In collaboration with investigators at the California Institute of Technology, Karoly Mirnics, M.D., and colleagues recently identified a component of the maternal immune response that may help set the stage for developing these disorders.

In the Journal of Neuroscience, the investigators report that a single injection of an immune protein — the cytokine interleukin-6 (IL-6) — during mid-gestation in mice induces behavior and tissue abnormalities reminiscent of schizophrenia and autism in the offspring. In pregnant mice with “fake infections,” they found that blocking IL-6 action prevented the behavioral deficits. The findings suggest that IL-6 may mediate the effects of maternal immune activation on the developing brain, predisposing the fetus to developing schizophrenia and/or autism.

— Melissa Marino

Getting a charge out of lasers

Electricity is the communication medium of nerve cells. Traditionally, researchers have generated neuronal electrical currents, or action potentials, by zapping neurons with tiny jolts of electricity. Recently, E. Duco Jansen, Ph.D., and colleagues have shown that pulses of laser light can also generate neuronal action potentials capable of making an attached muscle contract.

In the October Biophysical Journal, the researchers show that laser light stimulates rat sciatic nerves by transiently increasing their temperature. The team used their findings to work out the number and duration of pulses needed to safely stimulate the nerve.

Through a licensing agreement with a medical device company, this information is now being used to help develop a portable, hand-held laser capable of safely and effectively generating a motor or sensory response. A first generation research device is available, and the authors suggest that the technology will be able to help patients in the foreseeable future.

— Melissa Marino

Past Aliquots

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