Gary M Fiskum

Publication Detail

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Neuron-specific conditional expression of a mitochondrially targeted fluorescent protein in mice.

Krish Chandrasekaran; Julie L Hazelton; Yu Wang; Gary Fiskum; Tibor Kristian (Profiled Authors: Gary M Fiskum; Tibor Kristian)

Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. kchan004@umaryland.edu
The Journal of neuroscience : the official journal of the Society for Neuroscience 2006;26(51):13123-7.

Mitochondrial dysfunction contributes to the pathophysiology of both acute and chronic neurodegenerative disorders. Quantification of mitochondrial bioenergetic properties generally requires the use of isolated brain mitochondria. However, the involvement of neuronal mitochondrial dysfunction in these disorders is limited by the lack of markers, and therefore isolation procedures, that distinguish neuronal compared with astrocyte mitochondria. To address this and other issues concerning neuronal mitochondria in the CNS, transgenic mice were generated that express a fluorescent protein targeted specifically to neurons. A neuron-specific promoter, CaMKIIalpha (calcium/calmodulin-dependent kinase IIalpha) driven tTA (tetracycline transactivator) mice were crossed with TRE (tetracycline responsive element) driven mitochondrial targeted enhanced yellow fluorescent protein (eYFP) mice. Expression of eYFP in the bigenic mouse brain was observed only in neuronal mitochondria of striatum, forebrain, and hippocampus and was enhanced by the removal of the tetracycline analog doxycycline (Dox) in the diet. The respiratory control ratio of synaptic and nonsynaptic mitochondria isolated from eYFP-expressing mice was the same as control mice, suggesting that neuronal mitochondria expressing eYFP maintain normal bioenergetic functions. More importantly, the development of Dox-inducible, neuron targeted mito/eYFP transgenic mice offer a unique in vivo model for delineating the participation of neuronal mitochondria in neuronal survival and death.

3 Originating Grant

• 1.

  Kristian, Tibor

  Separation of brain glial and neuronal mitochondria

  15 July 2005 - 30 April 2008

  NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

• 2.

  Fiskum, Gary

  Neuroprotection After Cardiac Arrest

  1 July 2004 - 30 June 2007

  NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

• 3.

  Fiskum, Gary

  Molecular Mechanisms of Ischemia Reperfusion Brain Injury

  1 May 1995 - 31 December 2008

  NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

Scientific Context

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