Project description:Purpose: Identify the specific transcriptome alterations in astrocytes and microglia isolated from mouse prefrontal cortex (PFC) following a chronic intermittent ethanol vapor exposure paradigm Methods: We performed RNA-sequencing on astrocytes, microglia, and total homogenate tissue isolated from the PFC of C57BL/6J mice following chronic intermittent ethanol vapor exposure Results: We identified common neuroimmune gene expression response between cell types in response to CIE, unique networks of correlated genes differentially expressed in specific cell types, along with candidate pathways, biological processes and highly connected cell-type specific genes Conclusions: This study sheds light on the cell-specific effects of chronic ethanol and provides novel molecular targets for understanding ethanol dependence
Project description:We examined microRNA expression profiles in amygdala (AMY), nucleus accumbens (NAC) and prefrontal cortex (PFC) of male C57BL/6J mice exposed to 4 cycles of chronic intermittent ethanol (CIE) vapor. Animals were sacrificed at 0, 8, and 120 hr following the last ethanol exposure.
Project description:Persistent changes in brain gene expression are hypothesized to underlie thealtered neural signaling producing abusive consumption in AUD. To identify brain regional gene expression networks contributing to progressive ethanol consumption, we performed microarray and scale-free network analysis of expression responses in a C57BL/6J mouse model utilizing chronic intermittent ethanol by vapor chamber (CIE) in combination with limited access oral ethanol consumption. The interaction of CIE and oral consumption was studied with Affymetrix microarrays. Gene expression was studied in medial prefrontal cortex, nucleus accumbens, hippocampus, bed nucleus of the stria terminalis, and central nucleus of the amygdala. Brain region expression networks were analyzed for ethanol-responsive gene expression, correlation with ethanol consumption and functional content using extensive bioinformatics studies.
Project description:To understand how chronic intermittent ethanol vapor exposure changes the RNA content of brain-derived extracellular vesicles, we isolated total RNA and used lncRNA/mRNA microarray analysis to examine differential expression following CIE exposure in male animals
Project description:To understand how chronic intermittent ethanol vapor exposure changes the RNA content of brain-derived extracellular vesicles, we isolated total RNA and used lncRNA/mRNA microarray analysis to examine differential expression following CIE exposure in female animals
Project description:Binge drinking is rising among aged adults (>65 years of age). The distinct effects of binge ethanol exposure on neurodegeneration in the aged brain are not well described. Using our model of intermittent binge ethanol exposure in young and aged mice, we investigated how binge ethanol expoure may promote neurodegenerative diease development. Spatial transcriptomics revealed that binge ethanol exposure enriched neurodegenerative disease pathways in the aged hippocampus, including tau hyperphosphorylation and neuronal death. These data suggest binge drinking during advanced aging may promote neurodegenerative disease development.
Project description:Repeated excessive alcohol consumption increases the risk of developing cognitive decline and dementia. Hazardous drinking among older adults further increases such vulnerabilities. In order to understand the molecular mechanisms underlying alcohol-induced cognitive deficits in older adults, we performed a chronic intermittent ethanol exposure paradigm (ethanol or water gavage every other day 10 times) in 8-week-old young adult and 70-week-old aged rats. While spatial memory retrieval ascertained by probe trials in the Morris water maze was not significantly different between ethanol-treated and water-treated rats in both age groups after the fifth and tenth gavages, behavioral flexibility was impaired in ethanol-treated rats than water-treated rats in the aged group but not in the young adult group. Further proteomic and phosphoproteomic analyses on their hippocampal tissues by tandem mass tag mass spectrometry revealed ethanol-treatment-associated proteomic and phosphoproteomic differences distinct to the aged rats, including the upregulations of Prkcd protein level, several of its phosphosites, and its kinase activity and the same aspects in Camk2a but downregulated, and were enriched in pathways involved in neurotransmission regulation, synaptic plasticity, neuronal apoptosis, and insulin receptor signaling. In conclusion, our behavioral and proteomic results added several candidate proteins and pathways potentially associated with alcohol-induced cognitive decline in aged adults.
Project description:We examined global gene expression profiles in amygdala (AMY), nucleus accumbens (NAC), prefrontal cortex (PFC) and Liver of male C57BL/6J mice exposed to 4 cycles of chronic intermittent ethanol (CIE) vapor. Animals were sacrificed at 0, 8, and 120 hr following the last ethanol exposure.
