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Impact of autophagy impairment on experience- and diet-related synaptic plasticity
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Lalo, Ulyana, Nezis, Ioannis P. and Pankratov, Yuriy (2022) Impact of autophagy impairment on experience- and diet-related synaptic plasticity. International Journal of Molecular Sciences, 23 (16). e9228. doi:10.3390/ijms23169228 ISSN 1422-0067.
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WRAP-impact-autophagy-impairment-experience-and-diet-related-synaptic-plasticity-2022.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (4Mb) | Preview |
Official URL: https://doi.org/10.3390/ijms23169228
Abstract
The beneficial effects of diet and exercise on brain function are traditionally attributed to the enhancement of autophagy, which plays a key role in neuroprotection via the degradation of potentially harmful intracellular structures. The molecular machinery of autophagy has also been suggested to influence synaptic signaling via interaction with trafficking and endocytosis of synaptic vesicles and proteins. Still, the role of autophagy in the regulation of synaptic plasticity remains elusive, especially in the mammalian brain. We explored the impact of autophagy on synaptic transmission and homeostatic and acute synaptic plasticity using transgenic mice with induced deletion of the Beclin1 protein. We observed down-regulation of glutamatergic and up-regulation of GABAergic synaptic currents and impairment of long-term plasticity in the neocortex and hippocampus of Beclin1-deficient mice. Beclin1 deficiency also significantly reduced the effects of environmental enrichment, caloric restriction and its pharmacological mimetics (metformin and resveratrol) on synaptic transmission and plasticity. Taken together, our data strongly support the importance of autophagy in the regulation of excitatory and inhibitory synaptic transmission and synaptic plasticity in the neocortex and hippocampus. Our results also strongly suggest that the positive modulatory actions of metformin and resveratrol in acute and homeostatic synaptic plasticity, and therefore their beneficial effects on brain function, occur via the modulation of autophagy.
| Item Type: | Journal Article | |||||||||
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| Subjects: | Q Science > QH Natural history > QH426 Genetics | |||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||
| SWORD Depositor: | Library Publications Router | |||||||||
| Library of Congress Subject Headings (LCSH): | Autophagic vacuoles, Cell death, Apoptosis, Neuroplasticity, Cognition -- Effect of exercise on, Exercise -- Psychological aspects, GABA -- Receptors | |||||||||
| Journal or Publication Title: | International Journal of Molecular Sciences | |||||||||
| Publisher: | M D P I AG | |||||||||
| ISSN: | 1422-0067 | |||||||||
| Official Date: | 17 August 2022 | |||||||||
| Dates: |
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| Volume: | 23 | |||||||||
| Number: | 16 | |||||||||
| Article Number: | e9228 | |||||||||
| DOI: | 10.3390/ijms23169228 | |||||||||
| Status: | Peer Reviewed | |||||||||
| Publication Status: | Published | |||||||||
| Access rights to Published version: | Open Access (Creative Commons) | |||||||||
| Date of first compliant deposit: | 26 August 2022 | |||||||||
| Date of first compliant Open Access: | 30 August 2022 | |||||||||
| RIOXX Funder/Project Grant: |
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