Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Zebrafish model of a learning and memory disorder shows better treatment

15.09.2014

Using a zebrafish model of a human genetic disease called neurofibromatosis (NF1), a team from the Perelman School of Medicine at the University of Pennsylvania has found that the learning and memory components of the disorder are distinct features that will likely need different treatment approaches. They published their results this month in Cell Reports.

NF1 is one of the most common inherited neurological disorders, affecting about one in 3,000 people. It is characterized by tumors, attention deficits, and learning problems. Most people with NF1 have symptoms before the age of 10. Therapies target Ras, a protein family that guides cell proliferation. The NF1 gene encodes neurofibromin, a very large protein with a small domain involved in Ras regulation.


These are zebrafish in a facility at Perelman School of Medicine.

Credit: Robert Press

Unexpectedly, the Penn team showed that some of the behavioral defects in mutant fish are not related to abnormal Ras, but can be corrected by drugs that affect another signaling pathway controlled by the small molecule cAMP. They used the zebrafish model of NF1 to show that memory defects – such as the recall of a learned task -- can be corrected by drugs that target Ras, while learning deficits are corrected by modulation of the cAMP pathway. Overall, the team's results have implications for potential therapies in people with NF1.

"We now know that learning and memory defects in NF1 are distinct and potentially amenable to drug therapy," says co-senior author Jon Epstein, MD, chair of the department of Cell and Developmental Biology. "Our data convincingly show that memory defects in mutant fish are due to abnormal Ras activity, but learning defects are completely unaffected by modulation of these pathways. Rather these deficits are corrected with medicines that modulate cAMP."

... more about:
»Medicine »NF1 »Zebrafish »cAMP »defects »deficits »disorder »humans »zebrafish

Over the last 20 years, zebrafish have become great models for studying development and disease. Like humans, zebrafish are vertebrates, and most of the genes required for normal embryonic development in zebrafish are also present in humans. When incorrectly regulated, these same genes often cause tumor formation and metastatic cancers.

Zebrafish have also become an ideal model for studying vertebrate neuroscience and behavior. In fact, co-senior author Michael Granato, PhD, professor of Cell and Developmental Biology, has developed the first high-throughput behavioral assays that measure learning and memory in fish. For example, Granato explains, "normal fish startle with changes in noise and light level by bending and swimming away from the annoying stimuli and do eventually habituate, that is get used to the alternations in their environment. But, NF1 fish mutants fail to habituate. However, after adding cAMP to their water, they do learn, and then behave like the non-mutant fish."

This clearly indicates that learning deficits in the NF1 mutant fish are corrected by adding various substances that boost cAMP signaling. "Our data also indicate that learning and memory defects are reversible with acute pharmacologic treatments and are therefore not hard-wired, as might be expected for a defect in the development of nerves," says Epstein. "This offers great hope for therapeutic intervention for NF1 patients."

###

Co-first authors Marc A. Wolman and Eric D. de Groh, Sean M. McBride, and Thomas A. Jongens, all from Penn, were also on the paper.

The work was funded by the National Heart, Lung and Blood Institute (R01 HL062974, HD 37975A11) and the National Institute of Mental Health (RO1 MH092257), the Department of Defense, the FRAXA Research Foundation, and the University of Pennsylvania Clinical Research Scholars Program.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 17 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2013 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; Chester County Hospital; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2013, Penn Medicine provided $814 million to benefit our community.

Karen Kreeger | Eurek Alert!
Further information:
http://www.uphs.upenn.edu/news/

Further reports about: Medicine NF1 Zebrafish cAMP defects deficits disorder humans zebrafish

More articles from Life Sciences:

nachricht Plant mothers talk to their embryos via the hormone auxin
17.07.2018 | Institute of Science and Technology Austria

nachricht Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides
16.07.2018 | Tokyo Institute of Technology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Subaru Telescope helps pinpoint origin of ultra-high energy neutrino

16.07.2018 | Physics and Astronomy

Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides

16.07.2018 | Life Sciences

New research calculates capacity of North American forests to sequester carbon

16.07.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>