scholarly journals The effects of n-6 polyunsaturated fatty acid deprivation on the inflammatory gene response to lipopolysaccharide in the mouse hippocampus

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Shoug M. Alashmali ◽  
Lin Lin ◽  
Marc-Olivier Trépanier ◽  
Giulia Cisbani ◽  
Richard P. Bazinet

Abstract Background Neuroinflammation is thought to contribute to psychiatric and neurological disorders such as major depression and Alzheimer’s disease (AD). N-6 polyunsaturated fatty acids (PUFA) and molecules derived from them, including linoleic acid- and arachidonic acid-derived lipid mediators, are known to have pro-inflammatory properties in the periphery; however, this has yet to be tested in the brain. Lowering the consumption of n-6 PUFA is associated with a decreased risk of depression and AD in human observational studies. The purpose of this study was to investigate the inflammation-modulating effects of lowering dietary n-6 PUFA in the mouse hippocampus. Methods C57BL/6 male mice were fed either an n-6 PUFA deprived (2% of total fatty acids) or an n-6 PUFA adequate (23% of total fatty acids) diet from weaning to 12 weeks of age. Animals then underwent intracerebroventricular surgery, in which lipopolysaccharide (LPS) was injected into the left lateral ventricle of the brain. Hippocampi were collected at baseline and following LPS administration (1, 3, 7, and 14 days). A microarray (n = 3 per group) was used to identify candidate genes and results were validated by real-time PCR in a separate cohort of animals (n = 5–8 per group). Results Mice administered with LPS had significantly increased Gene Ontology categories associated with inflammation and immune responses. These effects were independent of changes in gene expression in any diet group. Results were validated for the effect of LPS treatment on astrocyte, cytokine, and chemokine markers, as well as some results of the diets on Ifrd2 and Mfsd2a expression. Conclusions LPS administration increases pro-inflammatory and lipid-metabolizing gene expression in the mouse hippocampus. An n-6 PUFA deprived diet modulated inflammatory gene expression by both increasing and decreasing inflammatory gene expression, without impairing the resolution of neuroinflammation following LPS administration.

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 146 ◽  
Author(s):  
Antoni Sureda ◽  
Miquel Martorell ◽  
Maria del Mar Bibiloni ◽  
Cristina Bouzas ◽  
Laura Gallardo-Alfaro ◽  
...  

The aim of this study was to assess free fatty acids’ (FAs) ex vivo anti-/proinflammatory capabilities and their influence on inflammatory gene expression and H2O2 production by human peripheral blood mononuclear cells (PBMCs). Anthropometric and clinical measurements were performed in 26 participants with metabolic syndrome. Isolated PBMCs were incubated ex vivo for 2 h with several free fatty acids—palmitic, oleic, α-linolenic, γ-linolenic, arachidonic and docosahexaenoic at 50 μM, and lipopolysaccharide (LPS) alone or in combination. H2O2 production and IL6, NFκB, TLR2, TNFα, and COX-2 gene expressions were determined. Palmitic, γ-linolenic, and arachidonic acids showed minor effects on inflammatory gene expression, whereas oleic, α-linolenic, and docosahexaenoic acids reduced proinflammatory gene expression in LPS-stimulated PBMCs. Arachidonic and α-linolenic acids treatment enhanced LPS-stimulated H2O2 production by PBMCs, while palmitic, oleic, γ-linolenic, and docosahexaenoic acids did not exert significant effects. Oleic, α-linolenic, and docosahexaenoic acids induced anti-inflammatory responses in PBMCs. Arachidonic and α-linolenic acids enhanced the oxidative status of LPS-stimulated PBMCs. In conclusion, PBMC ex vivo assays are useful to assess the anti-/proinflammatory and redox-modulatory effects of fatty acids or other food bioactive compounds.


Lipids ◽  
2017 ◽  
Vol 52 (4) ◽  
pp. 315-325 ◽  
Author(s):  
Marine S. Da Silva ◽  
Pierre Julien ◽  
Jean-François Bilodeau ◽  
Olivier Barbier ◽  
Iwona Rudkowska

2018 ◽  
Vol 47 (1) ◽  
pp. 114-124 ◽  
Author(s):  
Anne Gro W. Rognlien ◽  
Embjørg J. Wollen ◽  
Monica Atneosen-Åsegg ◽  
Rajikala Suganthan ◽  
Magnar Bjørås ◽  
...  

Abstract Background 8-Oxoguanine DNA-glycosylase 1 (OGG1) and mutY DNA glycosylase (MUTYH) are crucial in the repair of the oxidative DNA lesion 7,8-dihydro-8-oxoguanine caused by hypoxia-reoxygenation injury. Our objective was to compare the gene expression changes after hypoxia-reoxygenation in neonatal Ogg1-Mutyh double knockout mice (OM) and wildtype mice (WT), and study the gene response in OM after hyperoxic reoxygenation compared to normoxic. Methods Postnatal day 7 mice were subjected to 2 h of hypoxia (8% O2) followed by reoxygenation in either 60% O2 or air, and sacrificed right after completed reoxygenation (T0h) or after 72 h (T72h). The gene expression of 44 a priori selected genes was examined in the hippocampus/striatum and lung. Results We found that OM had an altered gene response compared to WT in 21 genes in the brain and 24 genes in the lung. OM had a lower expression than WT of inflammatory genes in the brain at T0h, and higher expression at T72h in both the brain and lung. In the lung of OM, five genes were differentially expressed after hyperoxic reoxygenation compared to normoxic. Conclusion For the first time, we report that Ogg1 and Mutyh in combination protect against late inflammatory gene activation in the hippocampus/striatum and lung after neonatal hypoxia-reoxygenation.


2009 ◽  
Vol 284 (23) ◽  
pp. 15400-15407 ◽  
Author(s):  
Kelly L. Weaver ◽  
Priscilla Ivester ◽  
Michael Seeds ◽  
L. Douglas Case ◽  
Jonathan P. Arm ◽  
...  

2013 ◽  
Vol 305 (9) ◽  
pp. R978-R986 ◽  
Author(s):  
Joseph C. Biedenkapp ◽  
Lisa R. Leon

Heat stroke (HS) is characterized by a systemic inflammatory response syndrome (SIRS) consisting of profound core temperature (Tc) changes in mice. Encephalopathy is common at HS collapse, but inflammatory changes occurring in the brain during the SIRS remain unidentified. We determined the association between inflammatory gene expression changes in the brain with Tc disturbances during HS recovery in mice. Gene expression changes of heat shock protein (HSP)72, heme oxygenase (hmox1), cytokines (IL-1β, IL-6, TNF-α), cyclooxygenase enzymes (COX-1, COX-2), chemokines (MCP-1, MIP-1α, MIP-1β, CX3CR1), and glia activation markers (CD14, aif1, vimentin) were examined in the hypothalamus (HY) and hippocampus (HC) of control (Tc ∼ 36.0°C) and HS mice at Tc,Max (42.7°C), hypothermia depth (HD; 29.3 ± 0.4°C), and fever (37.8 ± 0.3°C). HSP72 (HY<HC) and IL-1β (HY only) were the only genes that showed increased expression at Tc,Max. HSP72 (HY < HC), hmox1 (HY < HC), cytokine (HY = HC), and chemokine (HY = HC) expression was highest at HD and similar to controls during fever. COX-1 expression was unaffected by HS, whereas HD was associated with approximately threefold increase in COX-2 expression (HY only). COX-2 expression was not increased during fever and indomethacin (COX inhibitor) had no effect on this Tc response indicating fever is regulated by other inflammatory pathways. CD14, aif1, and vimentin activation at HD coincided with maximal cytokine and chemokine expression suggesting glia cells are a possible source of brain cytokines and chemokines during HS recovery. The inflammatory gene expression changes during HS recovery suggest cytokines and/or chemokines may be initiating development or rewarming from hypothermia, whereas fever pathway(s) remain to be elucidated.


2007 ◽  
Vol 46 (6) ◽  
pp. 321-328 ◽  
Author(s):  
Danielle I. Shaw ◽  
Wendy L. Hall ◽  
Natasha R. Jeffs ◽  
Christine M. Williams

FEBS Journal ◽  
2014 ◽  
Vol 281 (9) ◽  
pp. 2228-2239 ◽  
Author(s):  
Hyun Kook Cho ◽  
So Young Kim ◽  
Seong Keun Yoo ◽  
Yung Hyun Choi ◽  
JaeHun Cheong

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