Multiple Sclerosis (MS) is a chronic inflammatory disease that affects the brain and spinal cord. Inflammation, demyelination, synaptic alteration, and neuronal loss are hallmarks detectable in MS. Experimental autoimmune encephalomyelitis (EAE) is an animal model widely used to study pathogenic aspects of MS. Autophagy is a process that maintains cell homeostasis by removing abnormal organelles and damaged proteins and is involved both in protective and detrimental effects that have been seen in a variety of human diseases, such as cancer, neurodegenerative diseases, inflammation, and metabolic disorders. This study is aimed at investigating the au-tophagy signaling pathway through the analysis of the main autophagic proteins including Be-clin-1, microtubule-associated protein light chain (LC3, autophagosome marker) and p62 also called sequestosome1 (SQSTM1, substrate of autophagy-mediated degradation), in the hippo-campus of EAE-affected mice. The Beclin-1, LC3 and p62 expressions and of the Akt/mTOR pathway were examined by western blot experiments after EAE treatment. The results demonstrated that Beclin-1 and LC3 II significantly decreased (indicating reduction of autophagosomes), and p62 level also significantly decreased (suggesting that autophagic flux increased) in EAE mice com-pared to control animals. In parallel, molecular analysis detected deregulation of the Akt/mTOR signaling. Immunofluorescence double-labeling images showed co-localization of NeuN (neu-ronal nuclear marker) and Beclin-1, LC3 and p62 throughout the CA1 and CA3 hippocampal subfields. Taken together, these data demonstrate that activation of autophagy occurs in the neurons of hippocampus in this experimental model.

Ceccariglia, S., Sibilia, D., Parolini, O., Michetti, F., Di Sante, G., Altered Expression of Autophagy Biomarkers in Hippocampal Neurons in a Multiple Sclerosis Animal Model, <<INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES>>, 2023; 2023/24 (17): 1-17. [doi:10.3390/ijms241713225] [https://hdl.handle.net/10807/258717]

Altered Expression of Autophagy Biomarkers in Hippocampal Neurons in a Multiple Sclerosis Animal Model

Ceccariglia, Sabrina
Primo
Writing – Review & Editing
;
Sibilia, Diego
Secondo
Methodology
;
Parolini, Ornella
Visualization
;
Michetti, Fabrizio
Penultimo
Supervision
;
2023

Abstract

Multiple Sclerosis (MS) is a chronic inflammatory disease that affects the brain and spinal cord. Inflammation, demyelination, synaptic alteration, and neuronal loss are hallmarks detectable in MS. Experimental autoimmune encephalomyelitis (EAE) is an animal model widely used to study pathogenic aspects of MS. Autophagy is a process that maintains cell homeostasis by removing abnormal organelles and damaged proteins and is involved both in protective and detrimental effects that have been seen in a variety of human diseases, such as cancer, neurodegenerative diseases, inflammation, and metabolic disorders. This study is aimed at investigating the au-tophagy signaling pathway through the analysis of the main autophagic proteins including Be-clin-1, microtubule-associated protein light chain (LC3, autophagosome marker) and p62 also called sequestosome1 (SQSTM1, substrate of autophagy-mediated degradation), in the hippo-campus of EAE-affected mice. The Beclin-1, LC3 and p62 expressions and of the Akt/mTOR pathway were examined by western blot experiments after EAE treatment. The results demonstrated that Beclin-1 and LC3 II significantly decreased (indicating reduction of autophagosomes), and p62 level also significantly decreased (suggesting that autophagic flux increased) in EAE mice com-pared to control animals. In parallel, molecular analysis detected deregulation of the Akt/mTOR signaling. Immunofluorescence double-labeling images showed co-localization of NeuN (neu-ronal nuclear marker) and Beclin-1, LC3 and p62 throughout the CA1 and CA3 hippocampal subfields. Taken together, these data demonstrate that activation of autophagy occurs in the neurons of hippocampus in this experimental model.
2023
Inglese
Ceccariglia, S., Sibilia, D., Parolini, O., Michetti, F., Di Sante, G., Altered Expression of Autophagy Biomarkers in Hippocampal Neurons in a Multiple Sclerosis Animal Model, <<INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES>>, 2023; 2023/24 (17): 1-17. [doi:10.3390/ijms241713225] [https://hdl.handle.net/10807/258717]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/258717
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