Enhancing Neurogenesis to Improve Brain Recovery After Stroke

• Applicant: Professor Dr. Federico Calegari, Ph.D.
• Subject Area: Experimental Models for the Understanding of Nervous System Diseases ; Molecular Biology and Physiology of Neurons and Glial Cells ; Cell Biology
• Term: from 2017 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 357484509

The ambition of this project is to provide a proof-of-principle showing that endogenous NSC can be used to promote recovery of brain function after injury or disease. Toward this aim, in the last three years my group spent considerable resources into generating and characterizing a mouse model that now provides an ideal and unprecedented tool allowing us to expand NSC in a temporally controlled and tissue-specific manner on demand. In this mouse line, enhanced neurogenesis was found to be particularly strong in the neurogenic niche of the SVZ. Interestingly, the SVZ is the major neurogenic niche that in the human brain contributes newborn neurons that integrate in the striatum throughout life. Moreover, a large body of evidence has shown that in animal models of disease the SVZ reacts to injury such as stroke by increasing neurogenesis and generating neurons that migrate to the ischemic area. Yet, this link between the two physiologically occurring phenomena of increased neurogenesis and partial recovery after stroke is purely correlative and evidence that a manipulation the enhances the former can promote the latter is entirely missing. The characterization of our model allowed us to demonstrate the long-term functional integration of extranumerary neurons and consequent improvement in cognitive function in physiological conditions. We now plan to extend this in a disease context to investigate if it also improves recovery in pathological conditions. If successful, this will provide a proof-of-principle that increasing the endogenous pool of NSC and neurogenesis can be used toward developing novel therapies of neurodegenerative disease.

• DFG Programme: Research Grants