Analyses of the direct effects of Interleukin-4 signaling in neural stem/progenitor cells in control and Alzheimer's mice

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Alzheimer's disease is the most common form of dementia among elderly individuals; however, there is no cure for this disease yet. Alzheimer's disease is characterized by the chronic loss of neurons and synapses in the cerebral cortex, and by a significant loss of brain mass in a progressive manner. Additionally, the neural stem/progenitor cells that have the capacity to generate more neurons cease to proliferate, and therefore cannot produce more neurons. All of these properties of an Alzheimer brain prevents a successful regeneration of our brains in disease conditions. An important aspect of regenerative therapies for Alzheimer's disease is to design novel and unconventional therapeutic approaches. One particular way might be to mobilize the endogenous neural stem/progenitor cells to enhance their proliferation rate and differentiation capacity. When combined with approaches aiming to increase the survival and integration of neurons into circuitry, elevated levels of newly born neurons might provide a regenerative input in a highly unfavorable neurodegenerative environment. Therefore, it is of utmost importance to understand the behavior of stem cells during neurodegeneration, and how they can be coaxed to produce more neurons.In zebrafish, we have identified an immune-related molecules, IL4, which increases the proliferation of NSPCs in Alzheimer's disease conditions. In this proposal, we will investigate the role of IL4 signaling in an Alzheimer mouse model, and will determine whether IL4 can act to restore the proliferative capacity of NSPCs in disease conditions. In overall, our investigations will be an important contribution to the neuroscience field as it has the potential to identify a neuroinflammatory crosstalk signal mechanism through IL4, which might impose proliferative ability to neural stem cells. Our work can contribute to regenerative medicine approaches in clinical efforts towards neurodegenerative diseases, and has the potential to constitute an important milestone for neuroinflammation research.