Molecular biologist Seth Grant discusses the lifespan of synapse proteins and its implications for aging, memory, and diseases. The podcast explores the role of molecular biology in neuroscience, the challenges of choosing research projects, and the complexities of synapses in vertebrates and invertebrates, including octopuses.
Proteins in synapses have varying lifespans, with longer lifespans associated with resistance to aging.
There is a wide range of synapse types and subtypes with different protein compositions, opening up possibilities for targeted therapies.
Mutations in genes encoding synaptic proteins play a significant role in mental illnesses, emphasizing the importance of understanding the molecular differences and developing effective treatments.
Deep dives
Synaptic Protein Lifetime and Its Implications for Aging
The recent paper published in Neuron titled 'A Brain Atlas of Synapse Protein Lifetime Across the Mouse Lifespan' explores the duration that proteins stay in synapses and how it relates to aging. By studying the protein lifetime in mouse synapses, the researchers found that synapses with long protein lifetimes are more resistant to aging, while those with short protein lifetimes are more vulnerable. These findings shed light on the changes that occur in the brain during normal aging and provide a new perspective on age-related memory decline. Further research is needed to understand the molecular differences between these synapses and their implications for memory and neurodegenerative diseases.
The Diversity and Complexity of Synapses in the Brain
Another key insight from the podcast episode is the vast diversity of synapses in the brain. Through extensive analysis of synaptic proteins, the researchers discovered that synapses have multiple types and subtypes with different protein compositions. This catalog of synapses provides a new understanding of the complexity of the brain and opens up possibilities for targeted therapies in diseases that affect specific synapse types. The episode also highlights the importance of molecular biology in neuroscience and the revolutionary impact it has had on our understanding of memory and behavior.
Synaptic Proteins and Their Implications for Mental Illness
The podcast episode discusses the significant role of synapses and synaptic proteins in mental illnesses like schizophrenia and autism. The mutations in genes encoding synaptic proteins can lead to impairments in synapse function and cognitive flexibility. The research conducted on mouse models with these mutations has provided valuable insights into the mechanisms behind these disorders. Understanding the molecular differences and the impact of mutations on synapses is crucial for the development of effective treatments for mental illnesses. The study of synaptic proteins holds great promise for improving our understanding and management of psychiatric disorders.
Protein turnover in synapses
Proteins in synapses, particularly in the brain, have relatively short lifetimes, lasting only a matter of weeks or days. However, this data was obtained from taking large brain chunks instead of individual synapses. To study protein turnover at the individual synapse level, researchers modified a gene to produce a protein with a binding site for a synthetic small molecule. By injecting mice with this molecule, they observed that the majority of synapses lose their labeled proteins within a couple of weeks. However, certain brain regions, particularly those involved in long-term memory storage, contain synapses with longer protein lifetimes, lasting for months.
Diversity in synapse proteins
Synapse proteins exhibit not only compositional differences but also differences in their lifetimes, leading to increased synapse diversity. The distribution of synapses with shorter protein lifetimes is found in brain regions responsible for controlling innate behaviors, ensuring their stability. On the other hand, synapses with longer protein lifetimes are predominantly found in the superficial layers of the cortex and certain regions of the hippocampus, which are associated with long-term memory storage. The gradual decrease in protein turnover rate as an organism ages suggests a progressive change in protein lifetimes throughout the lifespan.
This episode of Brain Science features the return of molecular biologist Seth Grant. We briefly review his decades of research into the complexity of the protein structure of the synapse and then we focus on his most recent paper, which describes how the life-span of synapse proteins appears to change as animals age. Grant reflects of the significance of this finding both for animal research and human medicine.
Papers discussed in this episode:
Bulovaite, E., Qiu, Z., Kratschke, M., Zgraj, A., Fricker, D. G., Tuck, E. J., Gokhale, R., Koniaris, B., Jami, S. A., Merino-Serrais, P., Husi, E., Mendive-Tapia, L., Vendrell, M., O'Dell, T. J., DeFelipe, J., Komiyama, N. H., Holtmaat, A., Fransén, E., & Grant, S. G. N. (2022). A brain atlas of synapse protein lifetime across the mouse lifespan. Neuron, 110(24), 4057–4073.e8. https://doi.org/10.1016/j.neuron.2022.09.009
Cizeron, M., Qiu, Z., Koniaris, B., Gokhale, R., Komiyama, N. H., Fransén, E., & Grant, S. G. N. (2020). A brainwide atlas of synapses across the mouse life span. Science (New York, N.Y.), 369(6501), 270–275. https://doi.org/10.1126/science.aba3163
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