Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

NPAS3 and NPAS1 Genes May be Linked to Psychosis

01.09.2004


Mice with specific genetic mutations exhibit behavior similar to human psychosis, report UT Southwestern Medical Center at Dallas researchers, providing further support to the notion of a genetic link to schizophrenia.



The researchers genetically engineered mice with a mutation in the gene NPAS3, a mutation in the gene NPAS1 or a mutation in both genes. Both genes encode proteins that switch other genes on and off in brain cells. “These mice display certain deficits that are potentially consistent with schizophrenia,” said Dr. Steven McKnight, chairman of biochemistry at UT Southwestern and senior author of the study that will appear in an upcoming issue of the Proceedings of the National Academy of Sciences and is to be posted online this week.

“It’s too early to tell whether the abnormal behavior we observed in these mutated mice can be directly connected with human disease. On the other hand, we find it intriguing that members of a Canadian family carrying a mutation in the human NPAS3 gene have been reported to suffer from schizophrenia.”


Normal mice in a pen will climb over each other and interact, but the mice with the genetic mutations fail to socialize in this way. Instead, the mutants dart about wildly, avoiding interaction with their normal siblings.

In addition, the mutant mice do not have a normal startle response, and have a distinct reduction of a protein called reelin in their brains. Other researchers have shown in postmortem examinations of the brain tissue of schizophrenics that these patients have a reduction in reelin, said Dr. McKnight.

Schizophrenics also have problems socializing and often have enhanced physical activity, similar to that of the mutant mice. An impaired startle response, Dr. McKnight said, also may lead to a schizophrenia diagnosis.

More than 2 million Americans are affected by schizophrenia, according to the National Institute of Mental Health. The illness may impair a person’s ability to manage emotions, interact with others and think clearly. Symptoms include hallucinations, delusions, disordered thinking and social withdrawal. Most schizophrenia patients suffer chronically or episodically throughout their lives, and one of every 10 people with schizophrenia eventually commits suicide.

“We recognize that the connection of our study to human psychosis or schizophrenia is very tenuous,” Dr. McKnight said. “It’s difficult to draw direct parallels between the simple behavioral abnormalities observed in the mutant mice and the complex, delusional cognitive defects that characterize human schizophrenia. Our results may turn out to have nothing to do with schizophrenia, or they could point to something more substantial.”

Little is known about the NPAS1 and NPAS3 genes. Both genes are expressed in brain cells called inhibitory interneurons. These neurons are smaller than the typical excitatory neurons, which pass electrical signals amongst themselves and act as the brain’s wiring. The role of inhibitory interneurons, on the other hand, is to dampen the activity of excitatory neurons.

The NPAS1 and NPAS3 proteins are transcription factors that can activate or deactivate other genes. Just which genes they may control is unclear, Dr. McKnight said. Dr. McKnight and his research team are currently investigating what genes and what kind of brain cells the NPAS1 and NPAS3 proteins are acting upon. Information about this particular chemical pathway could provide further clues to a genetic link with human psychosis.

Other UT Southwestern biochemistry researchers involved in the study were first authors Drs. Claudia Erbel-Sieler and Xinle Wu, both postdoctoral researchers, and Carol Dudley, senior research scientist; Sandi Jo Estill, research assistant, and Tina Han, research technician. Dr. Ramon Diaz-Arrastia, associate professor of neurology at UT Southwestern and researchers from the University of Mississippi, the University of Cincinnati Medical School and the Children’s Medical Center in Cincinnati also participated.

The research was supported, in part, by the National Institute of Mental Health, the McKnight Foundation for Neuroscience and the Morton H. Meyerson Tzedukah Fund.

| newswise
Further information:
http://www.utsouthwestern.edu

More articles from Life Sciences:

nachricht One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie

nachricht The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Magnetic nano-imaging on a table top

20.04.2018 | Physics and Astronomy

Start of work for the world's largest electric truck

20.04.2018 | Interdisciplinary Research

Atoms may hum a tune from grand cosmic symphony

20.04.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>