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Making the Brain Glow: In Vivo Bioluminescence Imaging to Study Neurodegeneration

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Abstract

Bioluminescence imaging (BLI) takes advantage of the light-emitting properties of luciferase enzymes, which produce light upon oxidizing a substrate (i.e., d-luciferin) in the presence of molecular oxygen and energy. Photons emitted from living tissues can be detected and quantified by a highly sensitive charge-coupled device camera, enabling the investigator to noninvasively analyze the dynamics of biomolecular reactions in a variety of living model organisms such as transgenic mice. BLI has been used extensively in cancer research, cell transplantation, and for monitoring of infectious diseases, but only recently experimental models have been designed to study processes and pathways in neurological disorders such as Alzheimer disease, Parkinson disease, or amyotrophic lateral sclerosis. In this review, we highlight recent applications of BLI in neuroscience, including transgene expression in the brain, longitudinal studies of neuroinflammatory responses to neurodegeneration and injury, and in vivo imaging studies of neurogenesis and mitochondrial toxicity. Finally, we highlight some new developments of BLI compounds and luciferase substrates with promising potential for in vivo studies of neurological dysfunctions.

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Abbreviations

AD:

Alzheimer disease

ALS:

Amyotrophic lateral sclerosis

Aβ:

Amyloid beta

AP:

Apyrimidinic

ATP:

Adenosine-5′-triphosphate

BBB:

Blood–brain barrier

BLI:

Bioluminescence imaging

BRET:

Bioluminescence resonance energy transfer

CaMKIIα:

Calcium/calmodulin-dependent protein kinase II alpha

CCD:

Charged-coupled device camera

CNS:

Central nervous system

Cluc:

C-terminal half of luc

CT:

Computed tomography

DHE:

Dihydroethidium

DCX:

Doublecortin

dox:

Doxycycline

EAE:

Experimental autoimmune encephalomyelitis

EGFR:

Epidermal growth factor receptor

FRET:

Fluorescence resonance energy transfer

FTLD:

Frontotemporal lobar degeneration

GAP-43:

Growth-associated protein 43

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

GFP:

Green fluorescent protein

GFAP:

Glial fibrillary acidic protein

HIF-1:

Hypoxia-inducible transcriptional factor 1

hTau40 (2N4R):

The longest human Tau isoform

hTau40/ΔK280:

Pro-aggregant variant of human Tau

hTau40/ΔK280/PP:

Anti-aggregant variant of human Tau

KA:

Kainic acid

LPS:

Lipopolysaccharide

luc:

Luciferase

MCAO:

Middle cerebral artery occlusion

mtDNA:

Mitochondrial DNA

MRI:

Magnetic resonance imaging

mutUNG1:

Mutated mitochondrial DNA repair enzyme

NFTs:

Neurofibrillary tangles

NMDA:

N-methyl-d-aspartic acid

NSC:

Neuronal stem cells

Nluc:

N-terminal half of luc

NF-κB:

Nuclear factor kappa B

OB:

Olfactory bulb

PD:

Parkinson disease

PET:

Positron emission tomography

p/s:

Photons per second

QDs:

Quantum dots

Rluc:

Renilla luciferase

ROS:

Reactive oxygen species

SBE:

Smad binding elements

SPECT:

Single-photon emission computed tomography

SVZ:

Subventricular zone

TauRD :

Repeat domain of human Tau

TDP-43:

Transactive response DNA-binding protein 43

TGF-β:

Transforming growth factor beta

TLR2:

Toll-like receptor II

tTA:

Transactivator

US:

Ultrasound

WT:

Wild type

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Acknowledgments

We thank Eckhard Mandelkow for stimulating discussions throughout this project and Astrid Sydow and Dorthe Matenia for helpful suggestions regarding this review. The work of the laboratory described here was supported by grants from MPG, DZNE, WellcomeTrust/MRC, and Tau Consortium.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. DZNE (German Center for Neurodegenerative Diseases), Ludwig-Erhard-Allee 2, 53175, Bonn, Germany

    Katja Hochgräfe & Eva-Maria Mandelkow

  2. CAESAR Research Center, Ludwig-Erhard-Allee 2, 53175, Bonn, Germany

    Eva-Maria Mandelkow

  3. Max-Planck-Institute for Neurological Research, Hamburg Outstation, c/o DESY, Notkestr. 85, 22607, Hamburg, Germany

    Katja Hochgräfe & Eva-Maria Mandelkow

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  1. Katja Hochgräfe
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  2. Eva-Maria Mandelkow
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Correspondence to Eva-Maria Mandelkow.

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Hochgräfe, K., Mandelkow, EM. Making the Brain Glow: In Vivo Bioluminescence Imaging to Study Neurodegeneration. Mol Neurobiol 47, 868–882 (2013). https://doi.org/10.1007/s12035-012-8379-1

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  • DOI: https://doi.org/10.1007/s12035-012-8379-1

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