May 10, 2019
Keio University School of Medicine
A research group led by Assistant Professor Yoshitaka Kase, Associate Professor Takuya Shimazaki, and Professor Hideyuki Okano of the Department of Physiology, Keio University School of Medicine, has elucidated the molecular mechanism underlying the age-related decline in neurogenic potential.
In mammals, new neurons are produced daily even in adults (a process called neurogenesis). However, it was known that the source of these cells, neural stem cells and neural progenitor cells (cells at the stage before differentiating into neurons), decrease with age, leading to a decline in neurogenesis. Yet, the reason why neural stem and progenitor cells decrease with aging has remained poorly understood until now.
This study, using mice, revealed that: 1) a protein called p38 acts exclusively on neural progenitor cells to activate their self-proliferation, and 2) a decrease in p38 expression in neural stem and progenitor cells with aging is a major cause of the decline in neurogenic potential.
In addition, by forcibly expressing p38 in the neural stem and progenitor cells in the subventricular zone of aged mice, where p38 expression was significantly reduced, the team successfully increased the number of neural progenitor cells specifically. This restored neurogenesis to levels comparable to those in young mice, promoted long-term neurogenesis, and prevented brain atrophy in the subventricular zone.
Previous research aimed at regenerating brains damaged by conditions like stroke has focused on activating neural stem cells to promote neurogenesis. However, this approach had a drawback: repeated division of neural stem cells led to their depletion, causing a sharp decline in neurogenesis. This study confirmed that since p38 promotes the self-proliferation of neural progenitor cells without affecting neural stem cells, it enables effective, long-term neural regeneration without causing the depletion of the neural stem cell pool.
The findings of this research are expected to have applications not only in the field of aging research but also in neural regeneration for various diseases caused by neuronal loss, such as stroke, dementia, and depression.
The results of this research were published in the online edition of the American scientific journal "Stem Cell Reports" on Friday, May 10, 2019 (JST).
For the full press release, please see below.