Project description:We performed RNA sequencing for hippocampus of neonatal mice that were exposed to sevoflurane. We treated a group of neonatal mice with 2.5% sevoflurane for 2 hours on day 6, 7, 8, 9 and treated another group on day 6, 7. On day 36, we collected RNA (both total RNA and polysome-associated RNA) from the hippocampus in the aforementioned two groups and the control group (i.e., without sevoflurane treatment). We prepared the sequencing libraries with the collected RNA and sent them to Illumina sequencing platform.
Project description:Numerous recent studies showed that early anesthesia during neurodevelopment may induce changes in specific behaviors. We further studied the effects of early anesthetic exposures regarding addiction behavior later in life. Postnatal day (PND) 16 C57BL/6 mice received ketamine anesthesia for 5 consecutive days. Addiction behavior was evaluated 1 week after anesthesia treatment. Neurological changes after repeated anesthesia were evaluated using high-performance liquid chromatography, RNA sequencing, electrophysiology studies. Repeated ketamine anesthesia during the critical neurodevelopment period increased the expression of genes involved with action potential, and induced excitatory/inhibitory (E/I) imbalance in hippocampal CA1 pyramidal neurons of male mice. Such neurological changes were associated with increases in drug-induced contextual addiction memory.
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 probe potential differences between awake and anesthesia microglia, we performed the single-cell RNA sequencing (scRNA-seq) . Microglia were isolated by FACS as CD11b high CD45 low cells from awake and anesthesia mouse brains.
Project description:In this study, we addressed the following questions: Which brain cell types are transcriptionally reprogrammed under anesthesia? What is the cell-type specific response to anesthesia? And how does the response change between WT and AD in mouse models? We profiled by single nucleus RNA-sequencing (snRNA-seq) of hippocampus brain region samples from awake and anesthetized wild-type (WT) and APP/PS1 AD mouse model. We found a strong and robust transcriptional switch in all glial cell types in the anesthetized mice and in specific neuronal sub-types. Comparing WT to AD mice uncovered an AD-specific transcriptional response to anesthesia in glial cells and in specific neuronal sub-types. These findings provide new insights on the molecular changes occurring in the anesthetized brain and how they are altered in AD.
Project description:Aging is associated with a general decline of cognitive functions, and it is widely accepted that this decline results from changes in expression of proteins involved in regulation of synaptic plasticity. However, several lines of evidence has accumulated that impaired function of aged brain may be related to significant alterations in the energy metabolism. In the current study, we employed the label-free „Total protein approach” (TPA) method to focus on similarities and differences in energy metabolism proteomes of young (1 month-old) and aged (22 month-old) murine brains. We quantified over 7,000 proteins in each of three analyzed brain structures: hippocampus, cerebral cortex and cerebellum. To the best of our knowledge, this is the most extensive quantitative proteomic description of energy metabolism pathways during physiological aging of mice. The analysis demonstrates that aging does not affect significantly the abundance of total proteins in the studied brain structures, however, the levels of proteins constituting energy metabolism pathways differ significantly between young and aged mice.
Project description:Wolfram syndrome is caused by mutations in the WFS1 gene. WFS1 protein dysfunction results in a range of neuroendocrine syndromes and is mostly characterized by juvenile-onset diabetes mellitus and optic atrophy. WFS1 has been shown to participate in membrane trafficking, protein processing and Ca2+ homeostasis in the endoplasmic reticulum. In the present study we aimed to find the transcriptomic changes influenced by Wfs1 in the hypothalamus and hippocampus using RNA-sequencing. We used WFS1-deficient mice as a model system to analyze the changes in transcriptional networks. The number of differentially expressed genes between hypothalami of WFS1-deficient (Wfs1KO) and wild-type (WT) mice was 43 and between hippocampi 311 with False Discovery Rate (FDR) <0.05. In hypothalamus of Wfs1KO mice one of the most upregulated genes was Avpr1a whilst Avpr1b was significantly upregulated in hippocampus. Trpm8 was the most upregulated gene in the hippocampus of Wfs1KO mice. The functional analysis revealed significant enrichment of networks and pathways associated with protein synthesis, cell-to-cell signaling and interaction, molecular transport, metabolic disease and nervous system development and function. In conclusion, the transcriptomic profiles of WFS1-deficient hypothalamus and hippocampus do indicate the activation of degenerative molecular pathways causing the clinical occurrences typical to Wolfram syndrome.