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Tytuł pozycji:

Mechanisms underlying the predictive power of high skeletal muscle uptake of FDG in amyotrophic lateral sclerosis

Tytuł :
Mechanisms underlying the predictive power of high skeletal muscle uptake of FDG in amyotrophic lateral sclerosis
Autorzy :
Cecilia Marini
Vanessa Cossu
Tiziana Bonifacino
Matteo Bauckneht
Carola Torazza
Silvia Bruno
Patrizia Castellani
Silvia Ravera
Marco Milanese
Consuelo Venturi
Sebastiano Carlone
Patrizia Piccioli
Laura Emionite
Silvia Morbelli
Anna Maria Orengo
Maria Isabella Donegani
Alberto Miceli
Stefano Raffa
Stefano Marra
Alessio Signori
Katia Cortese
Federica Grillo
Roberto Fiocca
Giambattista Bonanno
Gianmario Sambuceti
Pokaż więcej
Temat :
Amyotrophic lateral sclerosis
SOD1G93A mouse model
[18F]-Fluorodeoxyglucose
Skeletal muscle
Oxidative stress
Endoplasmic reticulum
Medical physics. Medical radiology. Nuclear medicine
R895-920
Źródło :
EJNMMI Research, Vol 10, Iss 1, Pp 1-16 (2020)
Wydawca :
SpringerOpen, 2020.
Rok publikacji :
2020
Kolekcja :
LCC:Medical physics. Medical radiology. Nuclear medicine
Typ dokumentu :
article
Opis pliku :
electronic resource
Język :
English
ISSN :
2191-219X
Relacje :
http://link.springer.com/article/10.1186/s13550-020-00666-6; https://doaj.org/toc/2191-219X
DOI :
10.1186/s13550-020-00666-6
Dostęp URL :
https://doaj.org/article/6776dde55de34117aebe900fc801c0e9
Numer akcesji :
edsdoj.6776dde55de34117aebe900fc801c0e9
Czasopismo naukowe
Abstract Background We recently reported that enhanced [18F]-fluorodeoxyglucose (FDG) uptake in skeletal muscles predicts disease aggressiveness in patients with amyotrophic lateral sclerosis (ALS). The present experimental study aimed to assess whether this predictive potential reflects the link between FDG uptake and redox stress that has been previously reported in different tissues and disease models. Methods The study included 15 SOD1G93A mice (as experimental ALS model) and 15 wildtype mice (around 120 days old). Mice were submitted to micro-PET imaging. Enzymatic pathways and response to oxidative stress were evaluated in harvested quadriceps and hearts by biochemical, immunohistochemical, and immunofluorescence analysis. Colocalization between the endoplasmic reticulum (ER) and the fluorescent FDG analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) was performed in fresh skeletal muscle sections. Finally, mitochondrial ultrastructure and bioenergetics were evaluated in harvested quadriceps and hearts. Results FDG retention was significantly higher in hindlimb skeletal muscles of symptomatic SOD1G93A mice with respect to control ones. This difference was not explained by any acceleration in glucose degradation through glycolysis or cytosolic pentose phosphate pathway (PPP). Similarly, it was independent of inflammatory infiltration. Rather, the high FDG retention in SOD1G93A skeletal muscle was associated with an accelerated generation of reactive oxygen species. This redox stress selectively involved the ER and the local PPP triggered by hexose-6P-dehydrogenase. ER involvement was confirmed by the colocalization of the 2-NBDG with a vital ER tracker. The oxidative damage in transgenic skeletal muscle was associated with a severe impairment in the crosstalk between ER and mitochondria combined with alterations in mitochondrial ultrastructure and fusion/fission balance. The expected respiratory damage was confirmed by a deceleration in ATP synthesis and oxygen consumption rate. These same abnormalities were represented to a markedly lower degree in the myocardium, as a sample of non-voluntary striated muscle. Conclusion Skeletal muscle of SOD1G93A mice reproduces the increased FDG uptake observed in ALS patients. This finding reflects the selective activation of the ER-PPP in response to significant redox stress associated with alterations of mitochondrial ultrastructure, networking, and connection with the ER itself. This scenario is less severe in cardiomyocytes suggesting a relevant role for either communication with synaptic plaque or contraction dynamics.
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