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In spite of its classic part as an immunosuppressant, there is a increasing literature demonstrating that CORT can prime hippocampal microglia (Frank et al., 2010a, 2014; Barrientos et al., 2015a) and potentiate the neuroinflammatory response to a subsequent inflammatory challenge (Frank et al., 2010a; Munhoz et al., 2010; Hains et al., 2011; Loram et al., 2011). Here, we demonstrate that short-term HFD consumption produces CORT elevations within the hippocampus, increases the expression of neuroinflammatory priming signals, potentiates the proinflammatory response to LPS, and causes a deficit in forming long-term memory. To test that this HFD-induced CORT boost is usually a important mechanism in this cascade, we administered title= journal.pone.0115303 the GR antagonist mifepristone in the time of HFD intake. If this title= jir.2014.0026 treatment would protect against an HFD-plus-LPS-induced potentiated neuroinflammatory response and memory impairment, this would provide new insight in to the mechanisms underlying the effect of HFD consumption on cognitive declines.Materials and MethodsAnimals Male Wistar rats (Harlan Laboratories) had been utilized. All animals have been three months of age and weighed betweeneNeuro.orgJuly/August 2016, three(four) e0113-16.New Research3 of275 and 375 g in the.Box 345, University of Colorado Boulder, Boulder, CO 80309-0345. E-mail: ruth.barrientos@colorado.edu. DOI:http://dx.doi.org/10.1523/ENEURO.0113-16.2016 Copyright ?2016 Sobesky et al. This can be an open-access post distributed under the terms with the Inventive Commons Attribution four.0 International, which permits unrestricted use, distribution and reproduction in any medium supplied that the original operate is appropriately attributed.a proinflammatory response there and causing behavioral modifications (Milanski et al., 2009; Maric et al., 2014). However, for causes that remain unclear, free fatty acids do not pass directly into the hippocampus (Milanski et al., 2009). Even though HFD consumption alone has been shown to induce proinflammatory gene expression in various brain regions, including hippocampus (Hansen et al., 1998; Thaler et al., 2012; Beilharz et al., 2014, 2016), it ought to be noted that these studies particularly incorporated a substantial sugar component in their high-fat diet program regimen, which may very well be a crucial factor. A CPI-203 larger physique of literature (from research working with saturated HFDs that usually do not have higher sugar contents, for example the present 1), suggests that hippocampal cells are primed by HFD consumption, and that a secondary challenge have to occur prior to neuroinflammatory cytokines are detected or memory impairments are observed (Boitard et al., 2014; Cai et al., 2014; Knight et al., 2014; Sobesky et al., 2014). These studies have shown that HFD consumption alone will not make elevated cytokine expression inside the brain, but does elevate microglial markers of activation. In addition, shortterm HFD consumption sensitizes the hypothalamus and hippocampus to over-respond to an immune challenge, like to lipopolysaccharide (LPS), and, in turn, produces functional impairments mediated by those brain regions. Nevertheless, little is identified regarding the mechanisms that mediate this short-term HFD-induced priming effect, and hence could be the focus from the present study. Right here, we explored the novel notion that short-term consumption of HFD would induce an elevation in hippocampal corticosterone (CORT), which would in turn prime the hippocampus to amplify its inflammatory response to a mild inflammatory challenge, lastly resulting in impairments in memory consolidation.