Project description:Lipids contribute to the structure, development, and function of healthy brains. Dysregulated lipid metabolism is linked to aging and diseased brains. However, our understanding of lipid metabolism in aging brains remains limited. Here we examined the brain lipidome of mice across their lifespan using untargeted lipidomics. Co-expression network analysis highlighted a progressive decrease in 3-sulfogalactosyl diacylglycerols (SGDGs) and SGDG pathway members, including the potential degradation products lyso-SGDGs. SGDGs show an age-related decline specifically in the central nervous system and are associated with myelination. We also found that an SGDG dramatically suppresses LPS-induced gene expression and release of pro-inflammatory cytokines from macrophages and microglia by acting on the NF-κB pathway. The detection of SGDGs in human and macaque brains establishes their evolutionary conservation. This work enhances interest in SGDGs regarding their roles in aging and inflammatory diseases and highlights the complexity of the brain lipidome and potential biological functions in aging.
Project description:ChIP-seq of Sox10 in spinal cord and sciatic nerve 2 independent Sox10 ChIP samples each for spinal cord (CNS) and sciatic nerve (PNS), with respective inputs
Project description:A screen of 5 anti-inflammatory compounds for their effects in explanted, cultured rat spinal cord slices. All injured (explanted) cords are cultured for 4 hrs.
Project description:A screen of 5 anti-inflammatory compounds for their effects in explanted, cultured rat spinal cord slices. All injured (explanted) cords are cultured for 4 hrs. Keywords: ordered
Project description:ChIP-seq of Sox10 in spinal cord and sciatic nerve was performed to determine shared and unique binding sites for Sox10 in oligodendrocytes and Schwann cells, respectively. Sox10 is required for both Schwann cell and oligodendrocyte development. In addition, differentiation of myelinating glia is dependent upon axonal signaling, so these studies were performed in vivo.
Project description:This SuperSeries is composed of the following subset Series: GSE40506: Genome-wide mapping of Olig2 targets in primary oligodendrocytes GSE40510: Expression data from Sip1 cKO and control mice spinal cord Refer to individual Series
Project description:Increased adipose tissue lipogenesis is associated with enhanced insulin sensitivity. Mice overexpressing the Glut4 glucose transporter in adipocytes have elevated lipogenesis and increased glucose tolerance despite being obese with elevated circulating fatty acids. Lipidomic analysis of adipose tissue revealed the existence of branched fatty acid esters of hydroxy fatty acids (FAHFAs) that were elevated 16- to 18-fold in these mice. FAHFA isomers differ by the branched ester position on the hydroxy fatty acid (e.g., palmitic-acid-9-hydroxy-stearic-acid, 9-PAHSA). PAHSAs are synthesized in vivo and regulated by fasting and high-fat feeding. PAHSA levels correlate highly with insulin sensitivity and are reduced in adipose tissue and serum of insulin-resistant humans. PAHSA administration in mice lowers ambient glycemia and improves glucose tolerance while stimulating GLP-1 and insulin secretion. PAHSAs also reduce adipose tissue inflammation. In adipocytes, PAHSAs signal through GPR120 to enhance insulin-stimulated glucose uptake. Thus, FAHFAs are endogenous lipids with the potential to treat type 2 diabetes.
Project description:Axon regeneration in the central nervous system (CNS) requires reactivating injured neurons’ intrinsic growth state and enabling growth in an inhibitory environment. Using an inbred mouse neuronal phenotypic screen, we find that CAST/Ei mouse adult dorsal root ganglion neurons extend axons more on CNS myelin than the other eight strains tested, especially when pre-injured. Injury-primed CAST/Ei neurons also regenerate markedly in the spinal cord and optic nerve more than those from C57BL/6 mice and show greater spouting following ischemic stroke. Heritability estimates indicate that extended growth in CAST/Ei neurons on myelin is genetically determined, and two whole-genome expression screens yield the Activin transcript Inhba as most correlated with this ability. These screens are presented here. Biological quadruplicate - Mouse tissue - Naïve Dorsal Root Ganglia (DRG) and 5 day post sciatic nerve crush DRG - x9 strains.
Project description:‘Big tau’, a longer isoform of tau is expressed in peripheral nervous system (PNS) and specific regions of the central nervous system (CNS). Big tau distribution across the human nervous system and pathophysiological role remains largely unknown. Here, using mass spectrometry, we demonstrate the big tau protein results from the insertion of exon 4a-long in the human MAPT sequence. We observed a central-to-peripheral gradient of big tau expression, lowest in the cortical brain region, followed by the cerebellum, then spinal cord, with the highest level in the human sciatic nerve (PNS). Interestingly, brain regions overlapping with relatively lower big tau are more susceptible to neurofibrillary tangle (NFT) formation. Furthermore, we found that CSF big tau levels did not change with CSF Aβ abnormalities in AD, unlike the CNS tau isoform, which increased significantly with concomitant Aβ and cognitive abnormalities. Our findings provide new insights into the basic biology of big tau in humans, crucial for understanding its pathophysiological functions.