The research finds that deleting the Nf1 gene in mice results in long-lasting improvements in neurogenesis, which in turn makes those in the test group more sensitive to the effects of antidepressants.
"The significant implication of this work is that enhancing neurogenesis sensitizes mice to antidepressants – meaning they needed lower doses of the drugs to affect 'mood' – and also appears to have anti-depressive and anti-anxiety effects of its own that continue over time," said Dr. Luis Parada, director of the Kent Waldrep Center for Basic Research on Nerve Growth and Regeneration and senior author of the study published in the Journal of Neuroscience.
Just as in people, mice produce new neurons throughout adulthood, although the rate declines with age and stress, said Dr. Parada, chairman of developmental biology at UT Southwestern. Studies have shown that learning, exercise, electroconvulsive therapy and some antidepressants can increase neurogenesis. The steps in the process are well known but the cellular mechanisms behind those steps are not.
"In neurogenesis, stem cells in the brain's hippocampus give rise to neuronal precursor cells that eventually become young neurons, which continue on to become full-fledged neurons that integrate into the brain's synapses," said Dr. Parada, an elected member of the prestigious National Academy of Sciences, its Institute of Medicine, and the American Academy of Arts and Sciences.
The researchers used a sophisticated process to delete the gene that codes for the Nf1 protein only in the brains of mice, while production in other tissues continued normally. After showing that mice lacking Nf1 protein in the brain had greater neurogenesis than controls, the researchers administered behavioral tests designed to mimic situations that would spark a subdued mood or anxiety, such as observing grooming behavior in response to a small splash of sugar water.
The researchers found that the test group mice formed more neurons over time compared to controls, and that young mice lacking the Nf1 protein required much lower amounts of anti-depressants to counteract the effects of stress. Behavioral differences between the groups persisted at three months, six months and nine months. "Older mice lacking the protein responded as if they had been taking antidepressants all their lives," said Dr. Parada.
"In summary, this work suggests that activating neural precursor cells could directly improve depression- and anxiety-like behaviors, and it provides a proof-of-principle regarding the feasibility of regulating behavior via direct manipulation of adult neurogenesis," Dr. Parada said.
Dr. Parada's laboratory has published a series of studies that link the Nf1 gene – best known for mutations that cause tumors to grow around nerves – to wide-ranging effects in several major tissues. For instance, in one study researchers identified ways that the body's immune system promotes the growth of tumors, and in another study, they described how loss of the Nf1 protein in the circulatory system leads to hypertension and congenital heart disease.
The current study's lead author is former graduate student Dr. Yun Li, now a postdoctoral researcher at the Massachusetts Institute of Technology. Other co-authors include Yanjiao Li, a research associate of developmental biology, Dr. Renée McKay, assistant professor of developmental biology, both of UT Southwestern, and Dr. Dieter Riethmacher of the University of Southampton in the United Kingdom.
The study was supported by the National Institutes of Health's National Institute of Neurological Disorders and Stroke, and National Institute of Mental Health. Dr. Parada is an American Cancer Society Research Professor.
This news release is available on our World Wide Web home page at www.utsouthwestern.edu/home/news/index.html
To automatically receive news releases from UT Southwestern via email, subscribe at www.utsouthwestern.edu/receivenews
Deborah Wormser | EurekAlert!
'Lipid asymmetry' plays key role in activating immune cells
20.02.2018 | Biophysical Society
New printing technique uses cells and molecules to recreate biological structures
20.02.2018 | Queen Mary University of London
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
20.02.2018 | Life Sciences
20.02.2018 | Medical Engineering
20.02.2018 | Physics and Astronomy