The cellular mechanisms that promote long-term cell survival and maintenance of the adult nervous system are only poorly-understood, in spite of their clinical relevance. A study from the Hospital for Sick Children in Toronto and the University of Toronto has identified one such mechanism in brain stem cells that may be important for healthy cognitive aging.
The laboratories of Dr. David Kaplan and Freda Miller identified a gene called p63 that is required in mice for the ongoing survival of brain stem cells. Stem cells in the adult brain are thought to be necessary for some aspects of learning and memory, and may contribute to the repair of the injured and damaged brain. When they decreased the levels of p63 only in stem cells, there was a dramatic loss of those cells and the nerve cells that they produce. This loss resulted in an evident decline in learning and memory in those mice.
p63 is a relative of p53, a well-known suppressor of cancer that paradoxically can kill brain cells during injury and disease. In the normal brain, p63 functions by keeping the death-inducing activity of p53 in check, thereby ensuring that stem cells produce sufficient nerve cells to participate in new learning and memory tasks.
This study, published in the July 31, 2013 issue of the Journal of Neuroscience, is one of the first to identify a gene that plays a critical role in maintaining normal numbers of adult stem cells by managing their survival, thereby regulating important aspects of memory formation.
Drs. Sheena Josselyn and Paul Frankland at the Hospital for Sick Children in Toronto were important collaborators on this work, which was funded by the Canadian Institutes for Health Research and the Heart and Stroke Foundation of Canada. Dr. Kaplan is the Canada Research Chair in Cancer and Neuroscience, and Dr. Miller is the Canada Research Chair in Developmental Neurobiology and a Howard Hughes Medical Institute International Scholar.
Text by D Kaplan
Original research article: Cancino GI, Yiu AP, Fatt MP, Dugani CB, Flores ER, Frankland PW, Josselyn SA, Miller FD, Kaplan DR. p63 Regulates Adult Neural Precursor and Newly Born Neuron Survival to Control Hippocampal-Dependent Behavior. J Neurosci. 2013 Jul 31;33(31):12569-85. doi: 10.1523/JNEUROSCI.1251-13.2013. PubMed PMID: 23904595
