Stem cells activation in the brain is regulated by day and night
The discovery of Neural Stem Cells (NSCs) in the adult brain that have the remarkable capacity to produce new neurons raised an exciting possibility of using the endogenous regenerative capacity of the brain to repair brain damage and treat neurodegenerative diseases. Although promising, the use of NSCs to heal devastating diseases is far from a given, and further progress will depend on full understanding of the mechanisms that regulate NSCs activation. Indeed, uncontrolled NSCs proliferation may lead to the formation of brain tumors, while reduced activity may limit their regenerative capacities.
Understanding how NSCs transition from a quiescent state to a proliferative state to produce new brain cells is important not only for regenerative purposes, but also for deciphering how their function is tuned to different behavioral states. PhD Student Archana Gengatharan and colleagues, at the CERVO Brain Research Centre at Université Laval, used advanced imaging approaches to follow NSCs activation and division in freely behaving mice for several days up to months. Their results revealed that NSCs activation occurs mostly during the day, while darkness-induced melatonin signaling triggers NSCs quiescence. These live imaging approaches allowed them to capture how external stimuli regulate NSCs activation and this technology made it possible to investigate how other environmental cues affect NSCs physiology.
The second major advance in this study was the discovery of Ca2+ signatures of quiescent and active NSCs. They also showed that Ca2+ signaling decode and integrate distinct microenvironmental cues governing NSCs states. Interestingly, by using in vivo optogenetics to mimic the Ca2+ pattern of quiescent NSCs, they were able to reverse NSCs transition to proliferative state. In sum, the customized in vivo imaging approaches allowed Archana Gengatharan and colleagues to reveal key regulatory mechanisms governing NSCs activation in freely behaving mice.
Taken together these results further our understanding of the environmental and physiological cues that control the activation of adult neural stems cells. This activation underlies the adult mammalian brain’s remarkable capacity to produce new cells that integrate into pre-existing neural networks and that play a functional role in animal behavior. The results presented identify targets to activate neural stem cells in the brain in order to develop new strategies to repair brain damage and treat neurodegenerative diseases.
Dr. Archana Gengatharan
This work was Dr. Archana Gengatharan’s PhD project in Dr. Armen Saghatelyan’s laboratory at the CERVO Brain Research Centre – Université Laval. She was involved from the beginning of this project in the conceptualization, data curation and formal analysis. Dr. Gengatharan was also involved in the customization and establishment of several approaches, and teaching new PhD members of the lab to various methods that were established for this project. Dr. Gengatharan received her PhD in January 2020 and is now working as a medical science liaison in pharmaceutical industry.
This work was supported by an operating grant to Armen Saghatelyan from the Canadian Institutes for Health Research.
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