Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study links APC gene to learning and autistic-like disabilities

17.06.2014

New mouse model shows that APC regulates proteins critical for normal learning, memory, and behavior

Autistic-like behaviors and decreased cognitive ability may be associated with disruption of the function of the Adenomatous Polyposis Coli (APC) gene. When Tufts researchers deleted the gene from select neurons in the developing mouse brain, the mice showed reduced social behavior, increased repetitive behavior, and impaired learning and memory formation, similar to behaviors seen in individuals with autism and intellectual disabilities.

This study is the first to evaluate how the loss of APC from nerve cells in the forebrain affects brain development, learning, and behavior. The research team, led by Michele Jacob, Ph.D., engineered a new mouse model for studying cognitive and autistic-like disabilities. The study was published online today in Molecular Psychiatry.

In addition to observing autistic-like behaviors and cognitive impairments in the mice, researchers found significant molecular changes in the brain. Eliminating APC chiefly from the excitatory neurons in the forebrain led to altered levels of specific proteins that regulate gene expression and influenced the structure, number, and function of synapses.

Some of these molecular changes have not been seen in other genetic mouse models of cognitive and autistic-like disabilities, but are likely relevant to the human disorders based on recently identified risk genes. The researchers propose that APC tightly regulates particular protein levels, maintaining them within a range that is critical to normal learning and memory consolidation.

"What makes this study interesting is that although there are hundreds of risk genes implicated in autism, the removal of this single gene produced a multi-syndromic disorder similar to that seen in individuals with both cognitive deficits and autism. The APC-deficient mice are noticeably different from normal mice in their impaired learning, poor memory consolidation, repetitive behaviors, and reduced social interest," said co-first author Jonathan Alexander, a Ph.D. candidate in neuroscience at the Sackler School of Graduate Biomedical Sciences at Tufts and a member of the Michele Jacob lab at Tufts University School of Medicine.

"This APC knock-out mouse is different because APC is eliminated from a specific type of cell in the brain during a critical period of development. This leads to deregulation of key signaling pathways and produces the cognitive and behavioral changes that we observed," explained co-first author Jesse Mohn, Ph.D., a graduate of the Sackler School and now a scientist at Galenea Corp.

"APC loss leads to molecular changes predicted to resemble, at least in part, those caused by spontaneous mutations in another gene, CHD8, recently identified as a high confidence risk factor for sporadic autism, that is, autism that arises spontaneously rather than inherited genetic mutations from parents. Thus, our findings are relevant to autism and intellectual disabilities caused by other human gene mutations, not only APC," said senior author Michele Jacob, Ph.D., professor of neuroscience at Tufts University School of Medicine, and member of the Cell, Molecular and Developmental Biology; Cellular and Molecular Physiology; and Neuroscience program faculties at the Sackler School.

"This study demonstrates the vital role that APC plays as a central hub that links to and regulates multiple signaling pathways within nerve cells that are essential for normal cognition and social behavior," added Antonella Pirone, Ph.D., a co-author and postdoctoral scholar in the Jacob lab. "We hope that identifying these novel molecular and functional changes caused by APC loss will contribute to the development of effective treatments for autism and cognitive impairments in patients."

Tufts University has filed patent applications claiming the use of the new mouse model for the screening of improved therapeutics.

###

Additional authors on the study are Christina D. Palka, B.S., a summer undergraduate research assistant; So-Young Lee, Ph.D., formerly a member of the Phillip Haydon lab at Tufts University School of Medicine; Leslie Mebane, Ph.D., former member of the Jacob lab; and Phillip G. Haydon, Ph.D., the Annetta and Gustav Grisard professor and chair of neuroscience at Tufts University School of Medicine, and member of the neuroscience faculty at the Sackler School.

This research was supported by the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) under award numbers R01NS021725 and T32NS061764; and the National Institute of Deafness and other Communication Disorders (NIDCD) also of the NIH under award number R01DC008802. The Tufts Center for Neuroscience Research also supported this research through award number P30NS047243 from NINDS.

Mohn, JL, Alexander J, Pirone A, Palka CD, Lee S-Y, Mebane L, Haydon PG, Jacob MH, "Adenomatous polyposis coli protein deletion leads to cognitive and autism-like disabilities." Molecular Psychiatry, advance online publication, June 17, 2014, doi:10.1038/mp.2014.61

About Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences
Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts University are international leaders in innovative medical and population health education and advanced research. Tufts University School of Medicine emphasizes rigorous fundamentals in a dynamic learning environment to educate physicians, scientists, and public health professionals to become leaders in their fields. The School of Medicine and the Sackler School are renowned for excellence in education in general medicine, the biomedical sciences, and public health, as well as for innovative research at the cellular, molecular, and population health level. Ranked among the top in the nation, the School of Medicine is affiliated with six major teaching hospitals and more than 30 health care facilities. Tufts University School of Medicine and the Sackler School undertake research that is consistently rated among the highest in the nation for its effect on the advancement of medical and prevention science.

Siobhan E. Gallagher | Eurek Alert!

Further reports about: Biomedical Health Medicine Molecular Tufts cognitive consolidation disabilities mutations

More articles from Studies and Analyses:

nachricht Research investigates whether solar events could trigger birth defects on Earth
21.07.2015 | University of Kansas

nachricht Accounting for short-lived forcers in carbon budgets
15.07.2015 | International Institute for Applied Systems Analysis (IIASA)

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Glaciers melt faster than ever

Glacier decline in the first decade of the 21st century has reached a historical record, since the onset of direct observations. Glacier melt is a global phenomenon and will continue even without further climate change. This is shown in the latest study by the World Glacier Monitoring Service under the lead of the University of Zurich, Switzerland.

The World Glacier Monitoring Service, domiciled at the University of Zurich, has compiled worldwide data on glacier changes for more than 120 years. Together...

Im Focus: Quantum Matter Stuck in Unrest

Using ultracold atoms trapped in light crystals, scientists from the MPQ, LMU, and the Weizmann Institute observe a novel state of matter that never thermalizes.

What happens if one mixes cold and hot water? After some initial dynamics, one is left with lukewarm water—the system has thermalized to a new thermal...

Im Focus: On the crest of the wave: Electronics on a time scale shorter than a cycle of light

Physicists from Regensburg and Marburg, Germany have succeeded in taking a slow-motion movie of speeding electrons in a solid driven by a strong light wave. In the process, they have unraveled a novel quantum phenomenon, which will be reported in the forthcoming edition of Nature.

The advent of ever faster electronics featuring clock rates up to the multiple-gigahertz range has revolutionized our day-to-day life. Researchers and...

Im Focus: Superfast fluorescence sets new speed record

Plasmonic device has speed and efficiency to serve optical computers

Researchers have developed an ultrafast light-emitting device that can flip on and off 90 billion times a second and could form the basis of optical computing.

Im Focus: Unlocking the rice immune system

Joint BioEnergy Institute study identifies bacterial protein that is key to protecting rice against bacterial blight

A bacterial signal that when recognized by rice plants enables the plants to resist a devastating blight disease has been identified by a multi-national team...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Euro Bio-inspired - International Conference and Exhibition on Bio-inspired Materials

23.07.2015 | Event News

Clash of Realities – International Conference on the Art, Technology and Theory of Digital Games

10.07.2015 | Event News

World Conference on Regenerative Medicine in Leipzig: Last chance to submit abstracts until 2 July

25.06.2015 | Event News

 
Latest News

Reliable and extremely long-lasting – high-voltage power electronics for network expansion

04.08.2015 | Power and Electrical Engineering

Riding a horse is far more complex than riding simulators

04.08.2015 | Agricultural and Forestry Science

CO2 removal cannot save the oceans – if we pursue business as usual

04.08.2015 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>