Viader 2011 J Neurosci

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Viader A, Golden JP, Baloh RH, Schmidt RE, Hunter DA, Milbrandt J (2011) Schwann cell mitochondrial metabolism supports long-term axonal survival and peripheral nerve function. J Neurosci 31:10128-40.

» PMID: 21752989 Open Access

Viader A, Golden JP, Baloh RH, Schmidt RE, Hunter DA, Milbrandt J (2011) J Neurosci

Abstract: Mitochondrial dysfunction is a common cause of peripheral neuropathies. While the role of neuron and axonal mitochondria in peripheral nerve disease is well appreciated, whether Schwann cell (SC) mitochondrial deficits contribute to peripheral neuropathies is unclear. Here, we examine how SC mitochondrial dysfunction affects axonal survival and contributes to the decline of peripheral nerve function by generating mice with SC-specific mitochondrial deficits. These mice (Tfam-SCKOs) were produced through the tissue-specific deletion of the mitochondrial transcription factor A gene (Tfam), which is essential for mitochondrial DNA (mtDNA) transcription and maintenance. Tfam-SCKOs were viable, but as they aged, they developed a progressive peripheral neuropathy characterized by nerve conduction abnormalities as well as extensive muscle denervation. Morphological examination of Tfam-SCKO nerves revealed early preferential loss of small unmyelinated fibers followed by prominent demyelination and degeneration of larger-caliber axons. Tfam-SCKOs displayed sensory and motor deficits consistent with this pathology. Remarkably, the severe mtDNA depletion and respiratory chain abnormalities in Tfam-SCKO mice did not affect SC proliferation or survival. Mitochondrial function in SCs is therefore essential for maintenance of axonal survival and normal peripheral nerve function, suggesting that SC mitochondrial dysfunction contributes to human peripheral neuropathies.

Keywords: Schwann cell (SC), neuropathies, peripheral nerve function, Tfam-SCKOs mice, mitochondrial transcription factor A gene (Tfam)


Labels: MiParea: Respiration, mtDNA;mt-genetics, Genetic knockout;overexpression  Pathology: Neurodegenerative 

Organism: Mouse  Tissue;cell: Nervous system  Preparation: Intact cells  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase 

Coupling state: ROUTINE 

HRR: Oxygraph-2k