Effect of obesity on the neurovascular unit transcriptome in the female mice hippocampus using single nuclei RNA seq

Obesity is a global pandemic and a key risk factor for several neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease, or dementia. The neurovascular unit (NVU), essential for blood-brain barrier (BBB) integrity and comprised of endothelial cells, glial cells (microglia and astrocytes), and neurons, plays an important role in the pathogenesis of neurodegenerative diseases. However, molecular mechanisms underlying the effects of obesity on endothelial and other cells of and its contribution to neurodegeneration remains largely unknown, especially in females. In this study we aimed to decipher in-dept molecular modifications induced by obesity in cells of neurovascular unit by integrative multiomics analysis of endothelial cells, neurons, microglial cells, and astrocytes from the hippocampus of ob/ob female mice. Hippocampus were isolated from ob/ob and C57BL/6J female mice at 17-18 weeks of age. Gene expression profiles of cells of hippocampus were obtained using single nuclei RNA sequencing (snRNAseq) and data analyzed using in-depth bioinformatic analyses. Wild type (C57BL/6J) and ob/ob female mice were fed a standard purified diet AIN-93M, for 8 wks. Mice were sacrificed at 18 weeks of age and hippocampus was dissected from left hemisphere and then stored at -80 degree celcius. Hippocampal nuclei was isolated and single nuclei RNA sequencing was performed. Brain hippocampal endothelial cells, microglial cells, astrocytes, and neuronal cells gene expression was analyzed using a multiomic approach for differential expression of protein and non-protein coding genes, gene networks, functional pathways, and transcription factors.