TY - JOUR T1 - Up-regulation of neural and cell cycle-related microRNAs in brain of amyotrophic lateral sclerosis mice at late disease stage. AU - Marcuzzo,Stefania, AU - Bonanno,Silvia, AU - Kapetis,Dimos, AU - Barzago,Claudia, AU - Cavalcante,Paola, AU - D'Alessandro,Sara, AU - Mantegazza,Renato, AU - Bernasconi,Pia, Y1 - 2015/01/28/ PY - 2014/07/14/received PY - 2015/01/14/accepted PY - 2015/1/29/entrez PY - 2015/1/30/pubmed PY - 2016/1/20/medline SP - 5 EP - 5 JF - Molecular brain JO - Mol Brain VL - 8 N2 - 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. SN - 1756-6606 UR - https://www.unboundmedicine.com/medline/citation/25626686/Up_regulation_of_neural_and_cell_cycle_related_microRNAs_in_brain_of_amyotrophic_lateral_sclerosis_mice_at_late_disease_stage_ DB - PRIME DP - Unbound Medicine ER -