Spermidine protects from age-related synaptic alterations at hippocampal mossy fiber-CA3 synapses.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
23 12 2019
23 12 2019
Historique:
received:
10
09
2019
accepted:
06
12
2019
entrez:
25
12
2019
pubmed:
25
12
2019
medline:
5
11
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31873156
doi: 10.1038/s41598-019-56133-3
pii: 10.1038/s41598-019-56133-3
pmc: PMC6927957
doi:
Substances chimiques
Spermidine
U87FK77H25
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
19616Références
Mol Cell Biochem. 1995 Aug-Sep;149-150:271-8
pubmed: 8569740
Nat Neurosci. 2002 Jul;5(7):657-64
pubmed: 12055631
Cell Death Differ. 2015 Mar;22(3):509-16
pubmed: 25526088
J Neurosci Res. 2018 Mar;96(3):416-426
pubmed: 29230855
Nature. 1997 Aug 7;388(6642):590-3
pubmed: 9252190
Curr Biol. 2019 Feb 4;29(3):435-448.e8
pubmed: 30661803
Rejuvenation Res. 2012 Dec;15(6):590-5
pubmed: 22950434
J Neurosci. 2002 Jul 15;22(14):5840-7
pubmed: 12122046
PLoS Biol. 2016 Sep 29;14(9):e1002563
pubmed: 27684064
J Physiol. 2004 Jan 1;554(Pt 1):175-93
pubmed: 14678500
Nat Neurosci. 2013 Apr;16(4):449-55
pubmed: 23434911
Elife. 2019 Jul 16;8:
pubmed: 31309927
Cell. 2011 Sep 2;146(5):682-95
pubmed: 21884931
Nat Rev Neurosci. 2006 Jan;7(1):30-40
pubmed: 16371948
Neurobiol Aging. 2017 Jan;49:119-137
pubmed: 27794263
Science. 1997 Oct 17;278(5337):412-9
pubmed: 9334292
Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13304-9
pubmed: 8917586
J Neurochem. 1987 Mar;48(3):765-72
pubmed: 3806104
Front Synaptic Neurosci. 2010 Sep 22;2:139
pubmed: 21423525
Nature. 2010 Mar 25;464(7288):529-35
pubmed: 20336135
Nature. 1995 Sep 14;377(6545):115-8
pubmed: 7675078
Cell Metab. 2019 Mar 5;29(3):592-610
pubmed: 30840912
Cortex. 2018 Dec;109:181-188
pubmed: 30388439
Trends Neurosci. 2010 Mar;33(3):153-61
pubmed: 20071039
Cold Spring Harb Perspect Biol. 2012 May 01;4(5):
pubmed: 22357909
Neurosci J. 2013;2013:839535
pubmed: 26317100
Nature. 2016 Jan 7;529(7584):37-42
pubmed: 26738589
Nat Rev Neurosci. 2005 Nov;6(11):863-76
pubmed: 16261180
Front Cell Neurosci. 2014 Feb 04;8:28
pubmed: 24550783
Nat Neurosci. 2013 Oct;16(10):1453-60
pubmed: 23995066
Nat Rev Neurosci. 2012 Mar 07;13(4):240-50
pubmed: 22395804
Philos Trans R Soc Lond B Biol Sci. 2003 Apr 29;358(1432):765-72
pubmed: 12740124
Neurosci Lett. 2001 May 18;304(1-2):107-11
pubmed: 11335066
Nat Protoc. 2006;1(4):2075-81
pubmed: 17487197
J Neurosci. 1998 Jan 15;18(2):634-40
pubmed: 9425005
Proc Natl Acad Sci U S A. 2018 May 22;115(21):5594-5599
pubmed: 29735711
Science. 1994 Sep 23;265(5180):1878-82
pubmed: 7916482
Adv Exp Med Biol. 1975;53:171-83
pubmed: 164102
EMBO J. 2006 Jun 21;25(12):2856-66
pubmed: 16763567
Science. 2018 Jan 26;359(6374):
pubmed: 29371440
Nat Rev Neurosci. 2006 Apr;7(4):278-94
pubmed: 16552414
J Neurosci. 1988 Apr;8(4):1096-111
pubmed: 3357011
Nat Cell Biol. 2009 Nov;11(11):1305-14
pubmed: 19801973
Nat Med. 2016 Dec;22(12):1428-1438
pubmed: 27841876
J Physiol. 2003 Apr 15;548(Pt 2):425-38
pubmed: 12588898
Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14164-9
pubmed: 20660724
J Neurosci. 2007 Sep 26;27(39):10434-44
pubmed: 17898215
Neuroscience. 2015 Nov 19;309:1-16
pubmed: 26241337
J Cell Biol. 2011 Feb 21;192(4):615-29
pubmed: 21339330