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Updated: Jun 28, 2026
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Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology
Published on: March 23, 2011
Aging and alpha-synuclein affect synaptic plasticity in the dentate gyrus
Irina Gureviciene1, Kestutis Gurevicius, Heikki Tanila
1Department of Neurobiology, University of Kuopio, Neulaniementie 2, P.O. Box 1627, 70211, Kuopio, Finland. Irina.Gureviciene@uku.fi
Journal of Neural Transmission (Vienna, Austria : 1996)
|November 13, 2008
Summary
Overexpression of mutated alpha-synuclein (alpha-syn) in mice worsens aging effects and impairs synaptic plasticity, impacting brain function. This suggests alpha-syn plays a role in age-related neurodegeneration.
Area of Science:
- Neuroscience
- Molecular Biology
- Gerontology
Background:
- Intracellular alpha-synuclein (alpha-syn) accumulation is a hallmark of neurodegenerative diseases like Parkinson's.
- The normal function of alpha-syn, a presynaptic protein, remains largely unknown.
- Understanding alpha-syn's role is crucial for elucidating disease mechanisms and potential therapeutic targets.
Purpose of the Study:
- To investigate the role of alpha-syn in synaptic plasticity.
- To determine its contribution to age-related synaptic degeneration.
- To compare the effects of mutated alpha-syn overexpression versus normal aging in mice.
Main Methods:
- Utilized behavioral tests and electrophysiological measures in the dentate gyrus of adult and aged mice.
- Compared mice overexpressing mutated (A30P) human alpha-syn with non-transgenic littermates.
- Assessed basal synaptic transmission and long-term potentiation/depression.
Main Results:
- Aged mice exhibited decreased basal synaptic transmission and paired-pulse facilitation.
- Aged mice overexpressing mutated alpha-syn showed impaired long-term potentiation, leading to synaptic depression.
- These deficits were specific to aged mice with mutated alpha-syn accumulation.
Conclusions:
- Overexpression of mutated alpha-syn exacerbates the aging process in mice.
- Mutated alpha-syn leads to impaired synaptic plasticity, suggesting a role in age-related synaptic dysfunction.
- These findings highlight the detrimental impact of abnormal alpha-syn accumulation on neuronal function during aging.
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