Adult mice engineered to have more newborn neurons in their brain memory hub excelled at accurately discriminating between similar experiences – an ability that declines with normal aging and in some anxiety disorders.
Boosting such neurogenesis in the adult hippocampus also produced antidepressant-like effects when combined with exercise, in the study funded by the National Institutes of Health.
Researchers, for the first time, pinpointed the effects of enhanced adult neurogenesis by creating mice lacking a gene required for programmed cell death of newborn neurons in the adult hippocampus.
"These mice with more young neurons were better at recognizing patterns – tasks that become more challenging as we age," explained Rene Hen Ph.D., of Columbia University in New York City. "A deficit in this ability can also contribute to anxiety, as over-generalization sometimes leads to mistaking ambiguous cues as threatening. Our study demonstrates that the stimulation of adult neurogenesis is sufficient to improve such pattern recognition behavior, but, while necessary, not sufficient to lift depression-like behavior."
Hen and Amar Sahay, Ph.D., grantees of the NIH's National Institute of Mental Health (NIMH), and colleagues, report on their discovery online April 3, 2011, in the journal Nature.
"By helping to disentangle effects of enhanced neurogenesis on cognition from those on mood, this study brings us closer to understanding how it might be harnessed in the service of better treatments for disorders like depression, post traumatic stress syndrome and panic disorder, as well as for cognitive decline," said NIMH Director Thomas R. Insel, M.D.
In earlier studies, Hen and colleagues had shown that birth of new neurons in the hippocampus was necessary for the therapeutic effects of current antidepressant medications. Since it takes weeks for these cells to grow and become integrated into brain circuits, this helped to explain the delay in symptom improvement experienced by patients. Evidence has also emerged that environmental enrichment and exercise can also stimulate neurogenesis and produce antidepressant-like effects. Yet the exact contributions of increased adult neurogenesis remained elusive.
To identify them, the researchers used genetic engineering to create mice lacking a gene that normally kills off 50-80 percent of newborn neurons in the adult hippocampus. These mice with a relative surplus of adult-born neurons were champs at learning to discriminate between a chamber where they had previously received a foot shock and a similar-looking chamber that was safe. By contrast, mice in which adult hippocampal neurogenesis was blocked performed poorly at this fear discrimination learning task, often freezing in safe chambers.
Yet, the mice with genetically enhanced adult neurogenesis did not show improved anti-anxiety or antidepressant-like behaviors, such as increased exploration in anxiety-producing situations. Such behaviors emerged in these mice only after four weeks of wheel running exercise, suggesting that neurogenesis might need to be accompanied by some kind of environmental enhancement to produce such effects.
Hen and Sahay said they are now using neuronal growth factors in combination with enhanced neurogenesis to explore possible mechanisms underlying such anti-anxiety and antidepressant effects. They are also weighing emerging evidence that neurogenesis in the bottom part of the hippocampus influences mood and anxiety-related behaviors, while neurogenesis in the top part of the mouse brain structure may have more to do with thinking and memory.
Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Sahay A, Scobie KN, Hill AS, O'Carroll CM, Kheirbek MA, Burghardt NS, Fenton AA, Dranovsky A, Hen R. Nature. Epub 2011 Apr 3.
The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website, www.nimh.nih.gov.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
Jules Asher | EurekAlert!
Research team of the HAW Hamburg reanimated ancestral microbe from the depth of the earth
01.03.2017 | Hochschule für Angewandte Wissenschaften Hamburg
Researchers Imitate Molecular Crowding in Cells
01.03.2017 | Universität Basel
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.
On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
01.03.2017 | Health and Medicine
01.03.2017 | Physics and Astronomy
01.03.2017 | Life Sciences