Project description:Physical exercise stimulates adult hippocampal neurogenesis in mammals, and is considered a relevant strategy for preventing age-related cognitive decline in aging humans. However, its mechanism is controversial. Here, by investigating microRNAs (miRNAs) and their downstream pathways, we uncover that downregulation of miR-135a-5p mediates exercise-induced proliferation of adult NPCs in adult neurogenesis in the mouse hippocampus, likely by activation of phosphatidylinositol (IP3) signaling. Specifically, while overexpression of miR-135 prevents exercise-induced proliferation in the adult mouse hippocampus in vivo and in NPCs in vitro, its inhibition activates NPCs proliferation in resting and aged mice. Label free proteomics and bioinformatics analysis identifies 11 potential targets of miR-135 in NPCs, several of them involved in phosphatidylinositol signaling. Thus, miR-135a is key in mediating exercise-induced adult neurogenesis and opens intriguing perspectives toward the therapeutic exploitation of miR-135 to delay or prevent pathological brain ageing.Physical exercise stimulates adult hippocampal neurogenesis in mammals, and is considered a relevant strategy for preventing age-related cognitive decline in aging humans. However, its mechanism is controversial. Here, by investigating microRNAs (miRNAs) and their downstream pathways, we uncover that downregulation of miR-135a-5p mediates exercise-induced proliferation of adult NPCs in adult neurogenesis in the mouse hippocampus, likely by activation of phosphatidylinositol (IP3) signaling. Specifically, while overexpression of miR-135 prevents exercise-induced proliferation in the adult mouse hippocampus in vivo and in NPCs in vitro, its inhibition activates NPCs proliferation in resting and aged mice. Label free proteomics and bioinformatics analysis identifies 11 potential targets of miR-135 in NPCs, several of them involved in phosphatidylinositol signaling. Thus, miR-135a is key in mediating exercise-induced adult neurogenesis and opens intriguing perspectives toward the therapeutic exploitation of miR-135 to delay or prevent pathological brain ageing.
Project description:Neural progenitor cells (aNPCs) ensure lifelong neurogenesis in the mammalian hippocampus. Proper regulation of aNPC fate entails important implications for brain plasticity and healthy aging. Piwi proteins and the small noncoding RNAs interacting with them (piRNAs) are best known in gonads as repressors of transposons. Here, we show that Piwil2 (Mili) and piRNAs are abundant in aNPCs of the postnatal mouse hippocampus and demonstrate that this pathway is essential for proper neurogenesis. Particularly, depleting the piRNA pathway in aNPCs impaired neurogenesis while increasing senescence and the generation of reactive glia. Moreover, depletion of the piRNA pathway primarily elevated 5S ribosomal RNA, SINEB1 and mRNAs encoding ribosomal proteins and regulators of translation, resulting in higher polysome density and protein synthesis upon differentiation. Our results provide evidence of an essential role for the piRNA pathway in maintaining homeostasis to sustain neural stem cell fate, underpinning its possible involvement in brain plasticity and successful aging.
Project description:Transcriptome Sequencing During Mouse Brain Development Identifies Long Non-Coding RNAs Functionally Involved in Neurogenic Commitment
Project description:Long noncoding RNAs (lncRNAs) play important roles in brain function modulation and neurodegenerative diseases. However, whether lncRNA regulations are involved in the mechanisms of perioperative neurocognitive disorders (PNCD), especially in anesthesia related brain dysfunction, remains unknown. We explored the expression and regulation pattern profiles of lncRNAs in the hippocampus of aged rats after sevoflurane anesthesia with microarrays.
Project description:To examine fosB regulation of neurogenesis, depression and epilepsy, we compared the gene expression profiles of wild type, fosBd/d and fosB-null mice by microarray analysis. Microarray analysis revealed that genes related to neurogenesis, depression and epilepsy are altered in the hippocampus of fosB-null mice.
Project description:To examine fosB regulation of neurogenesis, depression and epilepsy, we compared the gene expression profiles of wild type, fosBd/d and fosB-null mice by microarray analysis. Microarray analysis revealed that genes related to neurogenesis, depression and epilepsy are altered in the hippocampus of fosB-null mice. Total RNA from the hippocampus of wild-type, fosBd/d and fosB-null mice was prepared using ISOGEN and RNeasy Mini kits. For DNA microarray experiments, total RNA (100ng) was added to poly-A control and treated with WT Expression Kit. cDNA was labeled using WT terminal labeling kit and hybridized with Affymetrix GeneChip Mouse Gene 1.0 ST platform (GPL6246).
Project description:Emerging evidence has shown that noncoding RNAs, particularly microRNAs (miRNAs), contribute to the pathogenesis of mood and anxiety disorders, although the molecular mechanisms are poorly understood. Here we show altered levels of miR-17-92 in adult hippocampal neural progenitors have a significant impact in neurogenesis and anxiety- and depression-related behaviors in mice. miR-17-92 deletion in adult neural progenitors causes a decrease, while its overexpression an increase of neurogenesis in the dentate gyrus, through regulating genes in the glucocorticoid pathway, especially serum- and glucocorticoid-inducible protein kinase-1 (Sgk1). miR-17-92 knockout mice show anxiety- and depression-like behaviors, whereas miR-17-92 overexpressing mice exhibit anxiolytic and antidepression-like behaviors. Furthermore, we show that miR-17-92 expression in the adult mouse hippocampus responds to chronic stress, and miR-17-92 rescues proliferation defects, induced by corticosterone, in hippocampal neural progenitors. Our study uncovers a crucial role for miR-17-92 in adult neural progenitors to regulate neurogenesis and anxiety- and depression-like behaviors.
Project description:Long noncoding RNAs (lncRNAs), which are noncoding RNAs (ncRNAs) with length more than 200 nucleotides (nt), have been demonstrated to be involved in various types of cancer. In this study, a custom designed microarray platform covering both mRNAs and lncRNAs was applied to tumor tissues of gastric, colon, liver and lung. 316 and 157 differential expressed (DE-) protein coding genes and lncRNAs common to these four types of cancer were identified respectively.