Published in Neuron, research from the lab of Juan Song, PhD, determined the cell-signaling role of a neuropeptide called cholecystokinin, which is important in regulating neural stem cells and creating adult-born neurons within the hippocampus of the brain.
The dentate gyrus is part of the hippocampus, an area of the brain that plays a critical role in memory formation and听contains neural stem cells and other niche cells,听such as granule cells, mossy cells, and astrocytes.听These niche cells can release signals that act on neural stem cells to regulate neurogenesis, the process of generating new neurons. The听, associate professor in the 黑料网 Department of Pharmacology, has been researching how certain local niche cells act on neural stem cells and regulate their behavior, but it has been unclear if and how these niche cells interact within the dentate gyrus to regulate neural stem cells.
, Song and colleagues addressed these challenges and reported the role of听听in the regulation of neural stem cells and neurogenesis within the hippocampus.
The researchers showed that stimulating a particular type of interneuron in the dentate gyrus 鈥� the cholecystokinin neuron 鈥� spurred neural stem cell depolarization via release of cholecystokinin neuropeptide. Moreover, cholecystokinin-induced neural stem cell depolarization required the activation of glutamate receptors on the neural stem cells. Cholecystokinin induced astrocytes to release glutamate, which acted on these glutamate receptors on the surface of stem cells. These actions ultimately increase the neurogenic potential of neural stem cells by promoting cell cycle progression via MAPK/ERK signaling.
Finally, the authors found that decreasing cholecystokinin release induced astrocyte reactivity and increased innate immune system processes. The resulting neuroinflammation lead to decreased neurogenic potential 听of neural stem cells, most likely through proinflammatory cytokine signaling.
鈥淭he surprising ways in which neuropeptides modulate circuits and astrocytes to link neuronal activity to neuroinflammatory conditions is still largely unknown鈥�, said first-author Brent Asrican, PhD, an assistant professor in the Song lab. 鈥淔uture studies towards this direction will untangle the complex relationships between brain circuitry and non-neuronal brain cells in health and disease states.鈥�
鈥淲e鈥檙e really excited about this study because we believe our findings have broad implications beyond adult neurogenesis,鈥� said Song, a member of the 黑料网 Neuroscience Center. 鈥淩ecent studies support the idea of reduced cholecystokinin in aged populations and patients with Alzheimer鈥檚 disease. Knowledge gained from our studies will help scientists create new treatment strategies by targeting these neuropeptide systems.鈥�
, a weekly blog about neuroscience research.