Health
Scientists have found that mitochondria at dysfunctional synapses cannot meet their energy needs, and can be powered too much or too little, leading to age-related cognitive impairment.
The brain is like a puzzle, requiring many nested and codependent pieces to function properly. The brain is divided into regions, each containing millions of neurons connected by thousands of synapses. These synapses, which enable communication between neurons, rely on smaller structures: message-sending boutons (bulging bulbs at the tips like branches of neurons), and message-receiving dendrites (boutons receiving messages). complementary branch-like structures for power supply), and power supply. – Generation of mitochondria. All these factors must be considered to create a cohesive brain.
However, in aging brains, these pieces can be lost or altered so that they no longer fit into the larger brain puzzle.
“50% of people experience a loss of working memory as they age, which reduces their ability to retain and manipulate information in the short term,” says co-lead author John Reynolds of the Salk Institute. Professor Courtney Gravis Bloom, Senior Staff Scientist, said. ‘Lab. “We set out to understand why some people maintain healthy working memory as they age and others do not. In the process, we uncovered novel mechanisms underlying the synaptic basis of cognitive impairment. Did.”
Previous studies have found that the brain loses synapses as it ages, and researchers have also seen this pattern in animal models. However, examination of the remaining synapses found evidence of disrupted coordination between bouton size and the mitochondria they contain. A fundamental neuroscience principle, the principle of ultrastructural size, explains that whenever the size of a part of a synaptic complex changes, so must the size. all other part. Synapses, mitochondria, boutons – all these parts need to scale with each other.Prior to the Salk Team study published in The forefront of aging neuroscience As of April 12, 2023, no one had questioned whether age or illness could violate this principle.
“To find out, we turned to electron microscopy,” says co-first author Casey Vanderlip, a former research assistant in the Reynolds lab. “This allowed us to visualize these components across many synapses. We found that synaptic loss occurs in healthy and impaired aging, but the difference is that Bouton It was a breakdown of the correlation between mitochondrial size and mitochondria.”
“This is a ripple effect, with immeasurably small synaptic structures altering neuronal networks, brain function, and behavior,” said Glavis-Bloom. “Investigating these microscopic dysfunctions is uncharted territory that could revolutionize our understanding of aging and its effects on cognition.”
The team found that adherence to the ultrastructural size principle is essential to avoid age-related impairments in working memory. By identifying violations of ultrastructural size principles and mitochondria-related impairments as key to age-related cognitive impairment, this study ushers in a new era in aging research.
“The synaptic images we capture are snapshots of dynamic processes,” says Reynolds, holder of the Fiona and Sanjay Jar Chairs in Neuroscience. “With these snapshots in hand, we can begin to think first about the mechanisms that coordinate the expansion and contraction of different parts of the synaptic complex. We can ask how we can explain the decline in function, which is completely new thinking about cognitive decline may lead to new goals for future treatments.”
Other authors include Sammy Weiser Novak and Uri Manor of the Salk Institute. Masaaki Kuwashima, Lindsey Kirk, and Kristen M. Harris of the University of Texas at Austin.
This research was supported by the American Heart Association and the Paul G. Allen Frontiers Group (19PABH134610000AHA), the National Institutes of Health (1R21AG068967-01, P30014195), and the Allen Initiative in Brain Health and Cognitive Impairment Awards jointly through the National Sciences. it was done. Foundation (2014862), Kavli Institute for Brain and Mind at UC San Diego (2021 Innovative Research Grant), Waite Foundation, Larry L. Hillblom Foundation, Don and Lorraine Freeberg Foundation, Conrad Previes Foundation.
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