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Cell Death Differ. 2016 Jan;23(1):18-28. doi: 10.1038/cdd.2015.39. Epub 2015 Apr 24.

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

Author information

1
Division of Neuropathology, Institute of Pathology, University Hospital Basel, Basel 4031, Switzerland.
2
Division of Neurophysiology, Institute of Physiology, Department of Biomedicine, University of Basel, Basel 4056, Switzerland.
3
Department of Neurosurgery, University Hospital Basel, Basel 4031, Switzerland.
4
Department of Biology, University of Padua, Padua 35121, Italy.
5
Proteomics Core Facility, Biozentrum, University of Basel, Basel 4056, Switzerland.
6
Neurobiology Laboratory for Brain and Mental Health, University Psychiatric University Clinics Basel, University of Basel, Basel 4012, Switzerland.
7
Dulbecco Telethon Institute IRCCS, San Raffaele Scientific Institute, Milan 20132, Italy.
8
Faculty of Biology and Medicine, Center for Integrative Genomics, University of Lausanne, Lausanne 1015, Switzerland.
9
Department of Protein Biochemistry, Institute of Life Science, Kurume University, Kurume 839-0864, Japan.
10
Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan.
11
Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, Padua 35129, Italy.

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.

PMID:
25909888
PMCID:
PMC4815974
DOI:
10.1038/cdd.2015.39
[Indexed for MEDLINE]
Free PMC Article

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