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Neuro

Mapping mRNAs in the brain

If the brain acts like a computer, which of the brain’s physical features store the information? Flashes of electricity may keep memories and sensations alive for the moment, but what plays the role that hard drives and CDs do for computers?

A simple answer could be: genes turning on and off, and eventually, neurons growing and changing their shapes. But it gets more complicated pretty quickly. Genes can be regulated at several levels:

  • at the level of transcription — whether messenger RNA gets made from a stretch of DNA in the cell’s nucleus
  • at the level of translation — whether the messenger RNA is allowed to make a protein
  • at the level of RNA localization — where the mRNAs travel within the cell

Each neuron has only two copies of a given gene but will have many dendrites that can have more or less RNA in them. That means the last two modes of regulation offer neurons much more capacity for storing information.

Gary Bassell, a cell biologist at Emory, and his colleagues have been exploring how RNA regulation works in neurons. They have developed special tools for mapping RNA, and especially, microRNA — a form of RNA that regulates other RNAs.

In the dendrites of neurons, FMRP seems to control where RNAs end up

In the dendrites of neurons, FMRP seems to control where RNAs end up

Fragile X mental retardation protein (FMRP), linked to the most common inherited form of mental retardation, appears to orchestrate RNA traffic in neurons. Bassell and pharmacologist Yue Feng recently received a grant from the National Institute of Child Health and Development to study FMRP’s regulation of RNA in greater detail. The grant was one of several at Emory funded through the American Recovery and Reinvestment Act’s support for the NIH.

In the video interview above, Bassell explains his work on microRNAs in neurons. Below is a microscope image, provided by Bassell, showing the pattern of FMRP’s localization in neurons.

Posted on by Quinn Eastman in Neuro Leave a comment

Next steps in progesterone for brain injury

At a recent Society for Neuroscience (SFN) meeting, Emory researchers described their efforts to learn about optimizing progesterone for treatment of traumatic brain injury.

Researcher Donald Stein, PhD, Asa G. Candler Professor of Emergency Medicine at Emory School of Medicine, has shown that progesterone can protect damaged brain tissue. Stein is director of the Department of Emergency Medicine’s Brain Research Laboratory.

Donald G. Stein, PhD

Donald G. Stein, PhD

One of the Emory SFN presentations covered efforts to find progesterone analogues that are more water soluble. This work comes from Stein and his colleagues in collaboration with the laboratory of Dennis Liotta, PhD, Emory professor of chemistry.

Currently, the lack of water solubility limits delivery of progesterone, in that the hormone must be prepared hours ahead and cannot be kept at room temperature. Small chemical modifications may allow similar compounds with the same effects as progesterone to be given to patients closer to the time of injury.

According to the results, two compounds similar to progesterone showed an equivalent ability to reduce brain swelling in an animal model of traumatic brain injury.

The second Emory report described evidence that adding vitamin D to progesterone enhances the hormone’s effectiveness when applied to neurons under stress in the laboratory. Like progesterone, vitamin D is a steroid hormone that is inexpensive, has good safety properties and acts on many different biochemical pathways.

David Wright, MD

David Wright, MD

The authors showed that a low amount of vitamin D boosted the ability of progesterone to protect neurons from excito-toxicity , a principal cause of brain injury and cell death.

A new study at Emory, slated to begin early 2010, will evaluate progesterone’s effectiveness for treating traumatic brain injury in a multisite phase III clinical trial called ProTECT III.

The study follows earlier findings that showed giving progesterone to trauma victims shortly after brain injury appears to be safe and may reduce the risk of death and long-term disability.

David Wright, MD, assistant professor of emergency medicine at Emory School of Medicine is the national study’s lead investigator.

Michael Frankel, MD, Emory professor of neurology, will serve as site principal investigator of the clinical trial at Grady Memorial Hospital.

Posted on by Quinn Eastman in Neuro Leave a comment

Voles and the neurochemistry of social behavior

A new study has shown that prairie voles may be a useful model in understanding the neurochemistry of social behavior. By influencing early social experience in prairie voles, researchers hope to gain greater insight into what aspects of early social experience drive diversity in adult social behavior.

VolesPrairie voles are small, highly social rodents that often form stable, life-long bonds between mates. In the wild, there is striking diversity in how offspring are reared. Some pups are reared by single-mothers, some by both parents (with the father providing much of the same care as the mother) and some in communal family groups.

Researchers Todd Ahern, a graduate student in the Emory Neuroscience Program, and Larry Young, PhD, professor of psychiatry and behavioral sciences at the Yerkes National Primate Research Center and Emory School of Medicine, compared pups raised by single mothers (SM) to pups raised by both parents (BP) to determine the effects of these types of early social environments on adult social behavior.

The study showed SM- and BP-reared animals experienced different levels of care during the neonatal period and that these differences significantly influenced bonding social behaviors in adulthood. Pups raised by single mothers were slower to make life-long partnerships, and they showed less interest in nurturing pups in their communal families.

Researchers also found differences in the oxytocin system. Oxytocin is best known for its roles in maternal labor and suckling, but, more recently, it has been tied to prosocial behavior, such as bonding, trust and social awareness. Very simply, altering their early social experience influenced adult bonding.

Further studies will look at the altered oxytocin levels in the brain to determine how these hormonal changes affect relationships.

Posted on by erios in Neuro Leave a comment
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