Impact of Cortical Spreading Depolarization on Neural Precursor Dynamics and Neurogenesis in the Adult Dentate Gyrus

• Applicants: Dr. Andreas Petzold; Anja Urbach, Ph.D.
• Subject Area: Experimental Models for the Understanding of Nervous System Diseases
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 574837824

Cortical spreading depolarizations (CSD) are waves of massive neuroglial mass depolarization that are highly prevalent in almost all forms of acute brain injury. Previous studies suggest that, in addition to their harmful effects on metabolically compromised brain areas, CSDs can be neuroprotective and promote plasticity and regeneration in surrounding and even remote well-supplied tissue. For instance, we have recently shown that CSD lead to a robust increase in adult hippocampal neurogenesis (AHN), a process involved in cognitive functions such as learning, memory, and mood regulation. Yet, it remains to be determined at what level CSDs exert their pro-neurogenic function, whether these changes are beneficial or detrimental to hippocampal function in the long-term, and through which mechanisms they modulate AHN. In the proposed project, we will employ a combination of immunohistology, genetic, behavioural and cutting-edge transcriptomic approaches to: i) investigate the impact of CSD on individual stages of AHN, from the proliferation of neural stem and progenitor cells to the integration of newly born neurons; ii) correlate CSD-induced changes in AHN with alterations in hippocampal function; and iii) determine the cell type-specific molecular mechanisms and intercellular interactions that orchestrate the neurogenic response to CSD. These investigations will provide crucial insights into the impact of CSD on AHN, clarifying its role in both disease progression and repair. This understanding is fundamental to the development of targeted and personalized therapies to improve patient outcomes in the context of acute brain injury.

• DFG Programme: Research Grants