Their findings, reported this week in the online version of the Proceedings of the National Academy of Sciences, challenge the notion that the time it takes for neurogenesis is the reason anti-depressant medications are not fully effective until three to five weeks after treatment begins.
The dentate gyrus of the brain's hippocampus is known to be where new neurons still form in adult mammals, and this region is thought to play a significant role in learning and memory, cognitive change with aging, depression and schizophrenia, and other brain processes, said Judy Cameron, Ph.D., professor, Department of Psychiatry, University of Pittsburgh School of Medicine, and senior scientist, Oregon National Primate Research Center, Oregon Health and Science University.
"Expanding our knowledge beyond rodent models to understand how neurons mature in non-human primates will give us more insight into what happens in the human brain," she said. "In rodents, neuronal maturation happens in four weeks, which is considerably different than what we have found in our monkey studies."
Dr. Cameron, co-senior scientist William T. Greenough, Ph.D., of the University of Illinois, and the team gave adult monkeys injections of an agent called BrdU, which gets incorporated into replicating DNA and thus serves as an indicator of new neuron formation. At different time points after the injections, they examined the brain tissue to look for markers of stages of maturation in tiny neurons called granule cells.
Six weeks after an injection, 84 percent of the new cells still bore markers of immaturity and were immature in shape; in a rodent, all of the cells would have matured by this time. Only a third of the monkey granule cells had markers of maturity up to 28 weeks after BrdU injections.
That means the majority of new granule cells will not reach maturity until more than six months have passed, Dr. Greenough and colleagues said. Also, because the human brain is larger than the monkey brain and takes longer to develop, maturation of adult human neurons would likely be further lengthened.
The longer period of new granule cell maturation in primates argues against the hypothesis, based on rodent models, that the onset of effectiveness of antidepressant medications at three to five weeks is related to neurogenesis and maturation of these cells.
The research team included Shawn J. Kohler and Gregory B. Stanton, Ph.D., of the University of Illinois; and Nancy I. Williams, Sc.D., of Pennsylvania State University. The study was funded by the National Institutes of Health, the Spastic Paralysis and Allied Diseases of the Central Nervous System Foundation, and the Retirement Research Foundation.
About the University of Pittsburgh School of Medicine
As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1997.
Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see www.medschool.pitt.edu.
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