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In vivo optical imaging of motor neuron autophagy in a mouse model of amyotrophic lateral sclerosis.
- Source :
-
Autophagy [Autophagy] 2011 Sep; Vol. 7 (9), pp. 985-92. Date of Electronic Publication: 2011 Sep 01. - Publication Year :
- 2011
-
Abstract
- Autophagy is involved in the pathological process of motor neuron death in amyotrophic lateral sclerosis (ALS). We have generated a novel double transgenic (DTg) mouse line by mating a green fluorescent protein (GFP)-fused microtubule-associated protein 1 light chain 3 (LC3) transgenic (LC3-Tg) mouse and a G93A mutant human Cu/Zn superoxide dismutase (mSOD1) transgenic (mSOD1-Tg) mouse. In vivo imaging of autophagy with these novel DTg mice was conducted at 10 (presymptomatic), 17 (early symptomatic) and 19 (late symptomatic) weeks of age. Fluorescence imaging analysis revealed a strong fluorescent signal in vivo over the T₃-S₁ level at 17 and 19 weeks of age only in the DTg mice. Ex vivo autophagy imaging of spinal cord sections (20 μm) also showed a progressive increase of the fluorescence signal from 17 to 19 weeks in DTg mice in the anterior horn at the L₄-₅ level, and the fluorescence signals were clearly observed in the gray matter of the spinal cord with a progressive increase of the signal and decreases in large motor neurons. Protein gel blot analysis revealed maximum LC3-I and LC3-II expressions at 19 weeks, consistent with the results from the in vivo autophagy imaging experiment. This method could also be applied as a unique tool for clarifying the role of autophagy, and to monitor the pathologic processes involving autophagy not only in ALS, but also other neurological diseases.
- Subjects :
- Animals
Astrocytes metabolism
Astrocytes pathology
Cell Count
Disease Models, Animal
Fluorescent Antibody Technique
Green Fluorescent Proteins metabolism
Humans
Mice
Mice, Transgenic
Microtubule-Associated Proteins metabolism
Phagosomes metabolism
Recombinant Fusion Proteins metabolism
Amyotrophic Lateral Sclerosis diagnosis
Amyotrophic Lateral Sclerosis pathology
Autophagy
Diagnostic Imaging methods
Motor Neurons pathology
Optical Phenomena
Subjects
Details
- Language :
- English
- ISSN :
- 1554-8635
- Volume :
- 7
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Autophagy
- Publication Type :
- Academic Journal
- Accession number :
- 21628996
- Full Text :
- https://doi.org/10.4161/auto.7.9.16012