Synaptic dysfunction, memory deficits and hippocampal atrophy due to ablation of mitochondrial fission in adult forebrain neurons.

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Version: Final published version
Serval ID
serval:BIB_BDF780D8E819
Type
Article: article from journal or magazin.
Collection
Publications
Title
Synaptic dysfunction, memory deficits and hippocampal atrophy due to ablation of mitochondrial fission in adult forebrain neurons.
Journal
Cell Death and Differentiation
Author(s)
Oettinghaus B., Schulz J.M., Restelli L.M., Licci M., Savoia C., Schmidt A., Schmitt K., Grimm A., Morè L., Hench J., Tolnay M., Eckert A., D'Adamo P., Franken P., Ishihara N., Mihara K., Bischofberger J., Scorrano L., Frank S.
ISSN
1476-5403 (Electronic)
ISSN-L
1350-9047
Publication state
Published
Issued date
2016
Volume
23
Number
1
Pages
18-28
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Well-balanced mitochondrial fission and fusion processes are essential for nervous system development. Loss of function of the main mitochondrial fission mediator, dynamin-related protein 1 (Drp1), is lethal early during embryonic development or around birth, but the role of mitochondrial fission in adult neurons remains unclear. Here we show that inducible Drp1 ablation in neurons of the adult mouse forebrain results in progressive, neuronal subtype-specific alterations of mitochondrial morphology in the hippocampus that are marginally responsive to antioxidant treatment. Furthermore, DRP1 loss affects synaptic transmission and memory function. Although these changes culminate in hippocampal atrophy, they are not sufficient to cause neuronal cell death within 10 weeks of genetic Drp1 ablation. Collectively, our in vivo observations clarify the role of mitochondrial fission in neurons, demonstrating that Drp1 ablation in adult forebrain neurons compromises critical neuronal functions without causing overt neurodegeneration.
Keywords
Animals, Antioxidants/administration & dosage, Atrophy/genetics, Atrophy/metabolism, Dynamins/biosynthesis, Dynamins/genetics, Hippocampus/growth & development, Hippocampus/metabolism, Memory Disorders/genetics, Memory Disorders/pathology, Mice, Mitochondria/metabolism, Mitochondria/pathology, Mitochondrial Dynamics/genetics, Nerve Degeneration/genetics, Nerve Degeneration/metabolism, Nervous System/growth & development, Nervous System/pathology, Neurons/metabolism, Neurons/pathology, Prosencephalon/growth & development, Prosencephalon/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
29/06/2015 11:14
Last modification date
20/08/2019 16:32
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