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Rodent Study Provides New Clues to Autism Origins

A new study on laboratory mice suggests reducing or limiting excessive levels of protein synthesis in the brain can limit autistic-like behaviors.

Researchers believe the findings may lead to the creation of pharmaceuticals aimed at treating autism spectrum disorders (ASD) that are associated with diminished social interaction skills, impaired communication ability, and repetitive behaviors.

The study is reported in the journal Nature.

“The creation of a drug to address ASD will be difficult, but these findings offer a potential route to get there,” said Eric Klann, Ph.D., a professor at New York University and the study’s senior author.

“We have not only confirmed a common link for several such disorders, but also have raised the exciting possibility that the behavioral afflictions of those individuals with ASD can be addressed.”

Researchers focused on the EIF4E gene, whose mutation is associated with autism. The mutation causing autism was proposed to increase levels of the eIF4E, the protein product of EIF4E, and lead to exaggerated protein synthesis.

Researchers believe overactive eIF4E signaling and exaggerated protein synthesis also may play a role in a range of neurological disorders, including fragile X syndrome (FXS).

In the study researchers examined mice with increased levels of eIF4E. They found that these mice had exaggerated levels of protein synthesis in the brain and exhibited behaviors similar to those found in autistic individuals—repetitive behaviors, such as repeatedly burying marbles, diminished social interaction, and behavioral inflexibility.

The researchers also found altered communication between neurons in brain regions linked to the abnormal behaviors.

To lessen these autistic-like behaviors, researchers tested a drug, 4EGI-1, which diminishes protein synthesis induced by the increased levels of eIF4E.

Investigators hypothesized that they could return the afflicted mice’s protein production to normal levels, and, with it, reverse autistic-like behaviors.

The subsequent experiments confirmed their hypotheses. The mice were less likely to engage in repetitive behaviors, more likely to interact with other mice, and were successful in navigating mazes that differed from those they previously solved, thereby showing enhanced behavioral flexibility.

Additional investigation revealed that these changes were likely due to a reduction in protein production—the levels of newly synthesized proteins in the brains of these mice were similar to those of normal mice.

“These findings highlight an invaluable mouse model for autism in which many drugs that target eIF4E can be tested,” added co-author Davide Ruggero, Ph.D., an associate professor at UCSF’s School of Medicine and Department of Urology. “These include novel compounds that we are developing to target eIF4E hyperactivation in cancer that may also be potentially therapeutic for autistic patients.”

Source: New York University

Rodent Study Provides New Clues to Autism Origins

Rick Nauert PhD

Rick Nauert, PhDDr. Rick Nauert has over 25 years experience in clinical, administrative and academic healthcare. He is currently an associate professor for Rocky Mountain University of Health Professionals doctoral program in health promotion and wellness. Dr. Nauert began his career as a clinical physical therapist and served as a regional manager for a publicly traded multidisciplinary rehabilitation agency for 12 years. He has masters degrees in health-fitness management and healthcare administration and a doctoral degree from The University of Texas at Austin focused on health care informatics, health administration, health education and health policy. His research efforts included the area of telehealth with a specialty in disease management.

APA Reference
Nauert PhD, R. (2015). Rodent Study Provides New Clues to Autism Origins. Psych Central. Retrieved on May 26, 2018, from https://psychcentral.com/news/2012/12/24/rodent-study-provides-new-clues-to-autism-origins/49632.html

 

Scientifically Reviewed
Last updated: 6 Oct 2015
Last reviewed: By John M. Grohol, Psy.D. on 6 Oct 2015
Published on PsychCentral.com. All rights reserved.