A comparative study of age-related changes in inhibitory processes and long-term potentiation in the lateral septum of mice

AbstractAging 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.

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Activation of p42 mitogen-activated protein kinase by arachidonic acid and trans-1-amino-cyclopentyl-1,3-dicarboxylate impacts on long-term potentiation in the dentate gyrus in the rat: analysis of age-related changes

Neuroscience ◽

10.1016/s0306-4522(98)00528-4 ◽

1999 ◽

Vol 90 (4) ◽

pp. 1167-1175 ◽

Cited By ~ 41

Author(s):

B. McGahon ◽

C. Maguire ◽

Á. Kelly ◽

M.A. Lynch

Keyword(s):

Arachidonic Acid ◽

Protein Kinase ◽

Dentate Gyrus ◽

Long Term Potentiation ◽

Mitogen Activated Protein Kinase ◽

Age Related ◽

Term Potentiation ◽

Mitogen Activated Protein ◽

Age Related Changes

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A Hippocampal NR2B Deficit Can Mimic Age-Related Changes in Long-Term Potentiation and Spatial Learning in the Fischer 344 Rat

Journal of Neuroscience ◽

10.1523/jneurosci.22-09-03628.2002 ◽

2002 ◽

Vol 22 (9) ◽

pp. 3628-3637 ◽

Cited By ~ 172

Author(s):

Daniel A. Clayton ◽

Michael H. Mesches ◽

Enriquez Alvarez ◽

Paula C. Bickford ◽

Michael D. Browning

Keyword(s):

Spatial Learning ◽

Long Term Potentiation ◽

Fischer 344 ◽

Age Related ◽

Term Potentiation ◽

Fischer 344 Rat ◽

Age Related Changes

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Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing

Molecular Psychiatry ◽

10.1038/s41380-021-01208-9 ◽

2021 ◽

Author(s):

Sujeong Yang ◽

Sylvain Gigout ◽

Angelo Molinaro ◽

Yuko Naito-Matsui ◽

Sam Hilton ◽

...

Keyword(s):

Chondroitin Sulphate ◽

Memory Loss ◽

Memory Deficits ◽

Long Term Potentiation ◽

Aged Mice ◽

Age Related ◽

Term Potentiation ◽

Early Memory

AbstractPerineuronal nets (PNNs) are chondroitin sulphate proteoglycan-containing structures on the neuronal surface that have been implicated in the control of neuroplasticity and memory. Age-related reduction of chondroitin 6-sulphates (C6S) leads to PNNs becoming more inhibitory. Here, we investigated whether manipulation of the chondroitin sulphate (CS) composition of the PNNs could restore neuroplasticity and alleviate memory deficits in aged mice. We first confirmed that aged mice (20-months) showed memory and plasticity deficits. They were able to retain or regain their cognitive ability when CSs were digested or PNNs were attenuated. We then explored the role of C6S in memory and neuroplasticity. Transgenic deletion of chondroitin 6-sulfotransferase (chst3) led to a reduction of permissive C6S, simulating aged brains. These animals showed very early memory loss at 11 weeks old. Importantly, restoring C6S levels in aged animals rescued the memory deficits and restored cortical long-term potentiation, suggesting a strategy to improve age-related memory impairment.

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