1. Spermidine protects from age-related synaptic alterations at hippocampal mossy fiber-CA3 synapses
- Author
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Eva Michael, David Toppe, Stephan J. Sigrist, Gaga Kochlamazashvili, Dietmar Schmitz, Bence Rácz, Franziska E. Müller, Alexander Wirth, Evgeni Ponimaskin, Alexander Stumpf, Rosanna P. Sammons, Marta Maglione, Sebastian J. Hofer, Laura Moreno-Velasquez, Frank Madeo, Tobias Eisenberg, Tanja Maritzen, Nikolaus Maier, Volker Haucke, and Andre Zeug
- Subjects
Aging ,Spermidine ,Long-Term Potentiation ,lcsh:Medicine ,Biology ,Hippocampal formation ,Neurotransmission ,Synaptic Transmission ,Synaptic vesicle ,Article ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Postsynaptic potential ,Animals ,lcsh:Science ,030304 developmental biology ,Hippocampal mossy fiber ,0303 health sciences ,Multidisciplinary ,musculoskeletal, neural, and ocular physiology ,lcsh:R ,Long-term potentiation ,Neural ageing ,CA3 Region, Hippocampal ,Cell biology ,nervous system ,chemistry ,Mossy Fibers, Hippocampal ,lcsh:Q ,Synaptic Vesicles ,Function and Dysfunction of the Nervous System ,Polyamine ,030217 neurology & neurosurgery - Abstract
Aging is associated with functional alterations of synapses thought to contribute to age-dependent memory impairment (AMI). While therapeutic avenues to protect from AMI are largely elusive, supplementation of spermidine, a polyamine normally declining with age, has been shown to restore defective proteostasis and to protect from AMI in Drosophila. Here we demonstrate that dietary spermidine protects from age-related synaptic alterations at hippocampal mossy fiber (MF)-CA3 synapses and prevents the aging-induced loss of neuronal mitochondria. Dietary spermidine rescued age-dependent decreases in synaptic vesicle density and largely restored defective presynaptic MF-CA3 long-term potentiation (LTP) at MF-CA3 synapses (MF-CA3) in aged animals. In contrast, spermidine failed to protect CA3-CA1 hippocampal synapses characterized by postsynaptic LTP from age-related changes in function and morphology. Our data demonstrate that dietary spermidine attenuates age-associated deterioration of MF-CA3 synaptic transmission and plasticity. These findings provide a physiological and molecular basis for the future therapeutic usage of spermidine.
- Published
- 2019