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Last modified: Wednesday, October 17, 2012

IU researchers discuss PTSD, predicting addiction treatment success and more at Neuroscience 2012

Dozens of Indiana University researchers participated in the Neuroscience 2012 scientific meeting in New Orleans Oct. 13-17. Below are examples of some of the research discussed.

IU scientists identify compounds that could thwart post-traumatic stress disorder

Anantha Shekhar

Anantha Shekhar

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A brain pathway that is stimulated by traumatic or fearful experiences can be disrupted by two compounds that show promise for preventing post-traumatic stress disorder, Indiana University researchers reported.

In a presentation prepared for the Neuroscience 2012 scientific conference, Anantha Shekhar and colleagues from IU reported the results of experiments with rats using a standard methodology called a conditioned fear test.

The neural signaling activated by fearful experiences -- a process that also is involved in learning and in memory formation -- begins when the neurotransmitter glutamate activates a receptor called NMDA, resulting in a later protein reaction involving production of nitrous oxide, another chemical messenger in the brain.

The two small molecules tested, known as IC87201 and ZL006, are known to disrupt such nitrous oxide production.

In the experiment, rats treated with either of the two compounds showed significantly less fear response than the untreated rats, the researchers reported.

The results, the researchers said, supported their hypothesis that the NMDA-mediated nitrous oxide production is important in successful formation of fear memories, and disrupting that interaction could potentially offer a means of preventing long-term post-traumatic stress disorder symptoms

Repeated intense activation of the brain network for fear makes it vulnerable to developing hypersensitivity, said Shekhar, Raymond E. Houk Professor of Psychiatry and director of the Indiana Clinical and Translational Sciences Institute.

"The majority of people who have a traumatic event, perhaps about 80 percent, will have some post-traumatic stress disorder symptoms for a few days. Only about 20 percent will have long-term problems, but currently there is no way to predict who those people will be," Shekhar said.

With that uncertainty, it would be appropriate to administer the treatment to all traumatized patients within a few hours of the incident, such as when a person arrives at an emergency room after an accident or a field hospital after a military incident, he said.

The next steps would be to optimize compounds and begin drug development efforts, Shekhar said.

Shekhar discussed "Post-trauma disruption of nNOS-PSD95 protein-protein interaction is an effective means to ameliorate conditioned fear," on Monday. Other Indiana University researchers involved in the work were Stephanie D. Fitz, Department of Psychology; Philip L. Johnson, assistant professor of anatomy and cell biology; Andrea G. Hohmann, Linda and Jack Gill Chair of Neuroscience and professor of psychological and brain sciences; Ted Widlanski, professor of chemistry; and Yvonne Y. Lai, Department of Psychological and Brain Sciences.

Relapse or recovery? Neuroimaging predicts course of substance addiction treatment

An Indiana University study has provided preliminary evidence that by measuring brain activity through the use of neuroimaging, researchers can predict who is likely to have an easier time getting off drugs and alcohol, and who will need extra help.

"We can also see how brain activity changes as people recover from their addictions," said Joshua Brown, assistant professor in the Department of Psychological and Brain Sciences at Indiana University Bloomington, part of the College of Arts and Sciences.

The chronic occurrence of relapse underscores the need for improved methods of treatment and relapse prevention. One potential cause for relapse is deficient self-regulatory control over behavior and decision-making. Specifically this lack of self-regulatory ability in substance dependent individuals has been associated with dysfunction of a mesolimbic-frontal brain network. Reduced activity within this self-regulatory brain network has previously been implicated in relapse, but the specific relationship between this network, self-regulatory ability and recovery is yet to be determined.

The current study explores neurophysiological and cognitive indicators of self-regulatory ability in a community-based sample of substance dependent individuals during the first three months of addiction treatment. The study tests participants' risk-taking inclinations through what is called a Balloon Analog Risk Task, a game in which the participants can decide whether to add increasing amounts of air to a balloon, gaining rewards until it pops. Those who took greater risks were shown to have reduced brain activity. By the same token, those who took less risk showed greater brain activity. By three months those who were successful in treatment also demonstrated a pattern of brain activation that coincided with the risk level of cues during the balloon risk task decision-making. In individuals who relapsed, risk-related activation was limited to certain brain regions, possibly signaling the anticipated reward rather than the risk of negative outcome.

The study, "Neural predictors and indicators of successful early recovery in substance dependent individuals," was discussed on Sunday. Co-authors are S.E. Forster; and Peter R. Finn, also of the Department of Psychological and Brain Sciences.

Study sheds light on role of exercise and androgens such as testosterone on nerve damage repair

Dale Sengelaub

Photo by Aaron Bernstein

Dale Sengelaub

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A study by researchers from Emory University and Indiana University found that the beneficial effects daily exercise can have on the regeneration of nerves also require androgens such as testosterone in both males and females. It is the first report of both androgen-dependence of exercise on nerve regeneration and of an androgenic effect of exercise in females.

"The findings will provide a basis for the development of future treatment strategies for patients suffering peripheral nerve injuries," said Dale Sengelaub, professor in the Department of Psychological and Brain Sciences at IU. "And they underscore the need to tailor those treatments differently for men and women."

Injuries to peripheral nerves are common. Hundreds of thousands of Americans are victims of traumatic injuries each year, and non-traumatic injuries, such as carpal tunnel syndrome, are found in even higher numbers. The researchers previously showed that two weeks of moderate daily exercise substantially improves regeneration of cut nerves and leads to functional recovery in mice, though different types of exercise are required to produce the effect in males and females. They now report that these beneficial effects of exercise require androgens such as testosterone in both males and females.

In the study they conducted, they exercised three groups of male and female mice. Nerves of the three groups were cut and surgically repaired. Once group received the drug flutamide, which blocks the androgen receptor. A second group received a placebo treatment. The third group was unexercised. Regenerating nerve fibers in the placebo group grew to more than twice the length of those in unexercised mice in both males and females. In flutamide-treated mice, the effects of exercise were blocked completely in both sexes.

The study, "Enhancement of peripheral axon regeneration by exercise requires androgen receptor signaling in both male and female mice," was discussed on Monday. Co-authors are Arthur W. English and Nancy Thompson, both from Emory University.

The Society of Neuroscience is promoting the study to media covering the conference as a "Hot Topic."

Physical activity shown to help young and elderly alike with lower-leg coordination

Rachel Ryder

Rachel Ryder

An Indiana University study that examined the effect of age and physical activity on lower leg muscle reflexes and coordination concluded that participation in physical activity was beneficial for lower leg muscle coordination across both sides of the body in both young and older study participants. Lower limb muscle communication is essential for everyday tasks, such as walking, balancing and climbing stairs.

"The results of this study suggest that participation in physical activity contributes to greater crossed-spinal reflex stability in both young and elderly subjects," said exercise scientist Rachel Ryder, a visiting research associate in the IU School of Public Health-Bloomington. "In other words, the two lower legs maintain stable muscular communication patterns, which could contribute to better coordination of muscles across the right and left side of the body. The lack of this coordination or stability could exacerbate fall risk in older, sedentary subjects."

Ryder's study involved 28 healthy men and women who were sorted by age into two groups: 14 subjects in a group of people 20 to 25 years old; the rest were over 65. Based on the International Physical Activity Questionnaire, the two groups were divided further into physically active or sedentary.

The researchers tested reflexes by alternately stimulating nerves in each leg with an electrical current while study participants rested in a prone position.

"Participation in physical activity could play an important role in maintaining the muscle reflex system in the lower limbs and assist in coordination throughout life," Ryder said. "This is particularly important in older adults. While voluntary movement has a large role to play in fall-prevention, the motor system's 'first line of defense' against a slip or trip is the reflex system. The muscle reflexes are capable of generating a motor response in under 50 milliseconds, allowing the reflex system to quickly correct for a sudden change in body position, or at the least, reduce the impact of the fall."

Ryder discussed her research on Wednesday. Her co-authors are Koichi Kitano and David Koceja from the Department of Kinesiology in the School of Public Health-Bloomington.

For additional assistance with these items, contact Tracy James at 812-855-0084 or Tweeting @Vitality_IU, with more news from IU at #IUNews and #IUMedNews; blogging Health & Vitality.