Project description:Chronic cerebral hypoperfusion (CCH) is a well-known risk factor for vascular dementia and other neurodegenerative disease, for which there are currently no effective medications available. MicroRNA (miRNA) are noncoding RNAS mediating post-translational silencing of genes, and has been extensively studied for their involvement in neurodegenerative disease. However, little is known about their roles in vascular dementia (VaD). In this work, a bilateral common carotid arteries occlusion (2-VO) surgery in rats was employed to induced CCH related cognitive dysfunction. Four months later, the hippocampi were dissected from 2-VO and sham operated rats for high-throughput profiling of miRNAs. Twelve differentially expressed miRNAs were identified according to a cutoff of |log2(Fold Change)|≥1 and p<0.05. GO analysis of target genes revealed that the most relevant biological processes included the regulatory region nucleic acid binding, histone acetyltransferase binding, organic acid transmembrane transporter activity, L-amino acid transmembrane transporter activity. The cellular structure mainly included histone deacetylation complexes, endosomes, Golgi membranes, etc. And the involved molecular processes mainly included axon development, organ morphogenesis, macromolecular modification, regulation of neuron projection development, neuron development. This study provides a framework for understanding the alternations in hippocampus miRNA profiles underwent hypoxia insult.
Project description:Little is understood about the underlying cellular and molecular mechanisms related to hippocampus damage and glial activation after severe cerebral hypoperfusion.Efforts to explore the relationship between neuropathological and gene expression changes support a role for identifying novel molecular pathways by transcriptomic mechanisms. To investigate hippocampus-specific transcriptome profiling after severe cerebral hypoperfusion in mice
Project description:Chronic cerebral hypoperfusion is manifested in various CNS diseases accompanied by cognitive impairment, such as dementia, however the precise mechanism of chronic cerebral hypoperfusion-induced cognitive impairment remains unknown. Recently, transient receptor potential ankyrin 1 (TRPA1), activated by oxidative stress, was reported to be involved in the cerebrovascular diseases, therefore we investigated the pathophysiological role of TRPA1 in chronic cerebral hypoperfusion using a mouse bilateral common carotid artery stenosis (BCAS) model. Early cognitive impairment and white matter injury was induced by BCAS in TRPA1-knockout (TRPA1-KO) but not wild-type (WT) mice. For further investigation into the involvement of TRPA1 in chronic cerebral hypoperfusion, we conducted RNA sequence (RNAseq) in the corpus callosum from sham- and BCAS-operated WT and TRPA1-KO mice.
Project description:Upregulation of neuronal PGC-1α ameliorates cognitive impairment induced by chronic cerebral hypoperfusion in mice. To investigate the underlying mechanism of PGC-1α, we have employed whole mRNA microarray expression profiling as a discovery platform to identify genes with the potential to change the hippocampal function. Indeed, PGC-1α overexpression alters the gene expression profiles of hippocampus, this suggested that neuronal PGC-1α might play an important role after chronic cerebral hypoperfusion.
Project description:PGC-1α overexpression in neurons protects against chronic cerebral hypoperfusion-induced cognitive impairment in mice. To investigate the neuroprotective mechanism of PGC-1α, we employed RNA-Seq analysis on PGC-1α-overexpressed HT-22 cells, a hippocampal neuron cell line. We performed OGD experiment to mimick chronic cerebral hypoperfusion. Indeed, PGC-1α overexpression alters the gene expression profiles of HT-22 cells, suggesting that neuronal PGC-1α might play an important role after chronic cerebral hypoperfusion.
Project description:To reveal the effects of Buyang Huanwu Decoction on circRNA-miRNA-mRNA transcriptional network of rats with cerebral ischemia, explore its molecular mechanism for the treatment of cerebral ischemia.
Project description:To investigate the Wuzang Wenyang Huayu Decoction Regulates Differentially Expressed Proteins in the Rat, Hippocampus after Cerebral Hypoperfusion.
Project description:We obtained the profiles of neuronal phosphoproteome after cerebral ischemia and reperfusion by isolating mice hippocampus. Hippocampus combined from either nine sham or nine focal cerebral ischemia 1.5 h and reperfusion 24 h (IR) mice were lysed, digested, labeled with different TMT tags, then pooled and analyzed by LC/LC-MS/MS. In total, we quantified 7,865 phosphopeptides,179 phosphorylation sites of 129 proteins were upregulated and 843 phosphorylation sites of 494 proteins were downregulated in hippocampus during cerebral ischemia 2 h compare with sham operation.
Project description:Accumulation of negative stressful life events caused major depressive disorder (MDD) a major public health problem related to disability around the world. For effective therapy and disease managements, a comprehensive genomic analysis to identify objective signatures is required to grasp pathophysiological changes and applicable markers. This data was from a chronic mild stress (CMS) induced MDD mouse model followed by Affmatrix cDNA expression array (GeneChip Mouse Genome 430 2.0 Array) analysis in amygdala, hippocampus, prefrontal cortex, and cerebral cortex.