Morphological correlates of synaptic protein turnover in the mouse brain

Author:

Li Fengxia12,Bahr Julius N234ORCID,Bierth Felicitas A-L235,Reshetniak Sofiia1ORCID,Tetzlaff Christian1,Fornasiero Eugenio F1,Wichmann Carolin23,Rizzoli Silvio O12ORCID

Affiliation:

1. Department of Neuro- and Sensory Physiology, University Medical Center Göttingen, Göttingen, Germany

2. Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany

3. Molecular Architecture of Synapses Group, Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany

4. Göttingen Graduate Center for Neurosciences, Biophysics and Molecular Biosciences (GGNB), University of Göttingen, Göttingen, Germany

5. Molecular Medicine Bachelor Programme, University Medical Center Göttingen, Göttingen, Germany

Abstract

Synaptic proteins need to be replaced regularly, to maintain function and to prevent damage. It is unclear whether this process, known as protein turnover, relates to synaptic morphology. To test this, we relied on nanoscale secondary ion mass spectrometry, to detect newly synthesized synaptic components in the brains of young adult (6 mo old) and aged mice (24 mo old), and on transmission electron microscopy, to reveal synapse morphology. Several parameters correlated to turnover, including pre- and postsynaptic size, the number of synaptic vesicles and the presence of a postsynaptic nascent zone. In aged mice, the turnover of all brain compartments was reduced by ∼20%. The turnover rates of the pre- and postsynapses correlated well in aged mice, suggesting that they are subject to common regulatory mechanisms. This correlation was poorer in young adult mice, in line with their higher synaptic dynamics. We conclude that synapse turnover is reflected by synaptic morphology.

Funder

Deutsche Forschungsgemeinschaft

Publisher

Life Science Alliance, LLC

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