Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective motor neuron degeneration in motor cortex, brainstem and spinal cord. microRNAs (miRNAs) are small non-coding RNAs that bind complementary target sequences and modulate gene expression; they are key molecules for establishing a neuronal phenotype, and in neurodegeneration. Here we investigated neural miR-9, miR-124a, miR-125b, miR-219, miR-134, and cell cycle-related miR-19a and-19b, in G93A-SOD1 mouse brain in pre-symptomatic and late stage disease. Results: Expression of miR-9, miR-124a, miR-19a and-19b was significantly increased in G93A-SOD1 whole brain at late stage disease compared to B6.SJL and Wt-SOD1 control brains. These miRNAs were then analyzed in manually dissected SVZ, hippocampus, primary motor cortex and brainstem motor nuclei in 18-week-old ALS mice compared to same age controls. In SVZ and hippocampus miR-124a was up-regulated, miR-219 was down-regulated, and numbers of neural stem progenitor cells (NSPCs) were significantly increased. In G93A-SOD1 brainstem motor nuclei and primary motor cortex, miR-9 and miR-124a were significantly up-regulated, miR-125b expression was also increased. miR-19a and-19b were up-regulated in primary motor cortex and hippocampus, respectively. Expression analysis of predicted miRNA targets identified miRNA/target gene pairs differentially expressed in G93A-SOD1 brain regions compared to controls. Conclusions: Hierarchical clustering analysis, identifying two clusters of miRNA/target genes, one characterizing brainstem motor nuclei and primary motor cortex, the other hippocampus and SVZ, suggests that altered expression of neural and cell cycle-related miRNAs in these brain regions might contribute to ALS pathogenesis in G93A-SOD1 mice. Re-establishing their expression to normal levels could be a new therapeutic approach to ALS.

Marcuzzo, S., Bonanno, S., Kapetis, D., Barzago, C., Cavalcante, P., D'Alessandro, S., et al. (2015). Up-regulation of neural and cell cycle-related microRNAs in brain of amyotrophic lateral sclerosis mice at late disease stage. MOLECULAR BRAIN, 8(1), 5 [10.1186/s13041-015-0095-0].

Up-regulation of neural and cell cycle-related microRNAs in brain of amyotrophic lateral sclerosis mice at late disease stage

BONANNO, SILVIA
Primo
;
2015

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective motor neuron degeneration in motor cortex, brainstem and spinal cord. microRNAs (miRNAs) are small non-coding RNAs that bind complementary target sequences and modulate gene expression; they are key molecules for establishing a neuronal phenotype, and in neurodegeneration. Here we investigated neural miR-9, miR-124a, miR-125b, miR-219, miR-134, and cell cycle-related miR-19a and-19b, in G93A-SOD1 mouse brain in pre-symptomatic and late stage disease. Results: Expression of miR-9, miR-124a, miR-19a and-19b was significantly increased in G93A-SOD1 whole brain at late stage disease compared to B6.SJL and Wt-SOD1 control brains. These miRNAs were then analyzed in manually dissected SVZ, hippocampus, primary motor cortex and brainstem motor nuclei in 18-week-old ALS mice compared to same age controls. In SVZ and hippocampus miR-124a was up-regulated, miR-219 was down-regulated, and numbers of neural stem progenitor cells (NSPCs) were significantly increased. In G93A-SOD1 brainstem motor nuclei and primary motor cortex, miR-9 and miR-124a were significantly up-regulated, miR-125b expression was also increased. miR-19a and-19b were up-regulated in primary motor cortex and hippocampus, respectively. Expression analysis of predicted miRNA targets identified miRNA/target gene pairs differentially expressed in G93A-SOD1 brain regions compared to controls. Conclusions: Hierarchical clustering analysis, identifying two clusters of miRNA/target genes, one characterizing brainstem motor nuclei and primary motor cortex, the other hippocampus and SVZ, suggests that altered expression of neural and cell cycle-related miRNAs in these brain regions might contribute to ALS pathogenesis in G93A-SOD1 mice. Re-establishing their expression to normal levels could be a new therapeutic approach to ALS.
Articolo in rivista - Articolo scientifico
G93A-SOD1 mice; MicroRNAs; Neural stem progenitor cells;
G93A-SOD1 mice; MicroRNAs; Neural stem progenitor cells; Amyotrophic Lateral Sclerosis; Animals; Brain; Cell Count; Cell Differentiation; Disease Progression; Hippocampus; Mice; Mice, Transgenic; MicroRNAs; Neural Stem Cells; Neuroglia; Neurons; Organ Specificity; RNA, Messenger; Superoxide Dismutase; Up-Regulation; Cell Cycle; Cellular and Molecular Neuroscience; Molecular Biology
English
5
Marcuzzo, S., Bonanno, S., Kapetis, D., Barzago, C., Cavalcante, P., D'Alessandro, S., et al. (2015). Up-regulation of neural and cell cycle-related microRNAs in brain of amyotrophic lateral sclerosis mice at late disease stage. MOLECULAR BRAIN, 8(1), 5 [10.1186/s13041-015-0095-0].
Marcuzzo, S; Bonanno, S; Kapetis, D; Barzago, C; Cavalcante, P; D'Alessandro, S; Mantegazza, R; Bernasconi, P
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/132176
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