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Sharpening Your Synapses: Spermidine Reverses Age Related Memory Decline

Summary: Researchers report administering spermidine can help to protect against age related synaptic changes and memory impairment.

Source: PLOS.

Synapses, connecting the neurons in our brains, continuously encode new memories, but the ability to form new memories (“learning”) diminishes drastically for many of us as we get older.

In the article published September 29 in open-access journal PLOS Biology, work by the groups of Stephan Sigrist from the Freie Universität Berlin, Andrea Fiala (Universität Göttingen) and Frank Madeo (Universität Graz) now shows that specific changes at the level of synapses directly provoke age-related dementia, and that, however, administering a simple substance already found in our bodies, spermidine, can help to avoid such age-related synaptic changes and thereby protect from age-induced memory impairment.

Just like humans, the fruit fly Drosophila melanogaster – a leading model for aging research – suffers from memory impairment with advancing age. The same team of researchers previously observed that Drosophila exhibits an age-induced decline in levels of spermidine, and that these memory deficits can be suppressed by feeding with a diet supplemented by spermidine.

They now describe an unexpected scenario that convincingly explains the suppression of memory deficits by spermidine feeding. In a nutshell, synapses within the Drosophila brain seem to narrow their operational space, and thus become increasingly unable to form new memories with age.

Dietary supplementation with spermidine, however, prevented these changes. Importantly, when the authors mimicked these age-associated changes by genetic means, learning suffered even in young flies, providing a causal link between generic synaptic mechanisms and age-induced memory impairment.

Image shows the plasma membrane.

Electron micrographs revealed the alignment of the plasma membrane, with evident increase in extracellular spacing between cellular elements, to be affected in 30d w1118 flies, when compared to 3d or 30dSpd w1118 flies. NeuroscienceNews.com image is credited to Gupta VK, Pech U, Bhukel A, Fulterer A, Ender A, Mauermann SF, et al.

This work promises to open up a new avenue when searching for new therapeutic strategies to fight age-associated dementia, a major health threat of our times.

About this memory research article

Funding: This work was supported by grants from the Bundesministerium für Bildung und Forschung (Smartage, 01GQ1420A) to SJS and CB, the Forschungszentrum für neurodegenerative Erkrankungen to SJS and AE, and the Deutsche Forschungsgemeinschaft to SJS and AB (Exc 257, TP A3 and A6 SFB 958; SFB 740 TP C09). UP and AF were supported by the German Research Foundation (SFB 889/B04) and the German Ministry of Research and Education via the Bernstein Center for Computational Neuroscience Göttingen (grant number 01GQ1005A). FM is grateful to the Austrian Science Fund FWF for grants P23490-B12, P24381, P 27893, I1000 and grant ‘SFB Lipotox’ and to BMWFW and the Karl-Franzens University for grant ‘Unkonventionelle Forschung’. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

Source: Stephan Sigrist – PLOS
Image Source: NeuroscienceNews.com image is credited to Gupta VK, Pech U, Bhukel A, Fulterer A, Ender A, Mauermann SF, et al.
Original Research: Full open access research for “Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release” by Varun K. Gupta, Ulrike Pech, Anuradha Bhukel, Andreas Fulterer, Anatoli Ender, Stephan F. Mauermann, Till F. M. Andlauer, Emmanuel Antwi-Adjei, Christine Beuschel, Kerstin Thriene, Marta Maglione, Christine Quentin, René Bushow, Martin Schwärzel, Thorsten Mielke, Frank Madeo, Joern Dengjel, André Fiala, and tephan J. Sigrist in PLOS Biology. Published online Septermber 29 2016 doi:10.1371/journal.pbio.1002563

Cite This NeuroscienceNews.com Article
PLOS “Sharpening Your Synapses: Spermidine Reverses Age Related Memory Decline.” NeuroscienceNews. NeuroscienceNews, 3 October 2016.
<http://neurosciencenews.com/spermidine-memory-aging-5178/>.
PLOS (2016, October 3). Sharpening Your Synapses: Spermidine Reverses Age Related Memory Decline. NeuroscienceNew. Retrieved October 3, 2016 from http://neurosciencenews.com/spermidine-memory-aging-5178/
PLOS “Sharpening Your Synapses: Spermidine Reverses Age Related Memory Decline.” http://neurosciencenews.com/spermidine-memory-aging-5178/ (accessed October 3, 2016).

Abstract

Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release

Memories are assumed to be formed by sets of synapses changing their structural or functional performance. The efficacy of forming new memories declines with advancing age, but the synaptic changes underlying age-induced memory impairment remain poorly understood. Recently, we found spermidine feeding to specifically suppress age-dependent impairments in forming olfactory memories, providing a mean to search for synaptic changes involved in age-dependent memory impairment. Here, we show that a specific synaptic compartment, the presynaptic active zone (AZ), increases the size of its ultrastructural elaboration and releases significantly more synaptic vesicles with advancing age. These age-induced AZ changes, however, were fully suppressed by spermidine feeding. A genetically enforced enlargement of AZ scaffolds (four gene-copies of BRP) impaired memory formation in young animals. Thus, in the Drosophila nervous system, aging AZs seem to steer towards the upper limit of their operational range, limiting synaptic plasticity and contributing to impairment of memory formation. Spermidine feeding suppresses age-dependent memory impairment by counteracting these age-dependent changes directly at the synapse.

“Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release” by Varun K. Gupta, Ulrike Pech, Anuradha Bhukel, Andreas Fulterer, Anatoli Ender, Stephan F. Mauermann, Till F. M. Andlauer, Emmanuel Antwi-Adjei, Christine Beuschel, Kerstin Thriene, Marta Maglione, Christine Quentin, René Bushow, Martin Schwärzel, Thorsten Mielke, Frank Madeo, Joern Dengjel, André Fiala, and tephan J. Sigrist in PLOS Biology. Published online Septermber 29 2016 doi:10.1371/journal.pbio.1002563

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