Role of activity-dependent neuronal metabolic plasticity in brain aging

• Applicant: Professor Dr. Joachim Kirsch, since 10/2023
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 431144153

Neuronal energy metabolism is crucial for brain function and is impaired in normal brain aging and neurodegenerative diseases. We recently identified a metabolic gene program that is induced by synaptic activity and promotes a shift of neuronal energy metabolism towards aerobic glycolysis. This metabolic shift is likely to improve bioenergetic robustness and to confer neuroprotection. We hypothesize that during brain aging, impaired synaptic function causes impaired expression of the metabolic gene program, and thus contributes to impaired energy metabolism and neuronal function. In this proposal, we will study activity-regulated gene expression and neuronal energy metabolism in vivo, in young and aged mice. Using virus-mediated gene transfer, we aim to rescue neuronal energy metabolism in aged mice and assess its impact on neuronal structure, energy metabolism, and cognitive abilities in vivo. In this proposal we use a careful balance of established methods such as enzyme- and immunohistochemistry, and novel methods such as imaging mass spectrometry, to ensure both a high probability of success and the potential for highly innovative results.

• DFG Programme: Research Grants
• Co-Investigators: Dr. Theodore Alexandrov; Professor Dr. Karsten Hiller; Professorin Dr. Ana M. M. Oliveira
• Ehemaliger Antragsteller: Professor Dr. Carlos Bas Orth, until 10/2023