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https://www.readbyqxmd.com/read/27167127/enriched-endogenous-omega-3-fatty-acids-in-mice-ameliorate-parenchymal-cell-death-after-traumatic-brain-injury
#1
Huixia Ren, Zhen Yang, Chuanming Luo, Haitao Zeng, Peng Li, Jing X Kang, Jian-Bo Wan, Chengwei He, Huanxing Su
Currently no effective therapies are available for the treatment of traumatic brain injury (TBI). Early intervention that specifically provides neuroprotection is of most importance which profoundly influences the outcome of TBI. In the present study, we adopted a closed-skull mild TBI model to investigate potential roles of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in protecting against TBI. Using two-photon laser scanning microscopy (2PLSM), parenchymal cell death and reactive oxidative species (ROS) expression were directly observed and recorded after TBI through a thinned skull bone window...
May 11, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/26677076/the-lipoxygenases-their-regulation-and-implication-in-alzheimer-s-disease
#2
Grzegorz A Czapski, Kinga Czubowicz, Joanna B Strosznajder, Robert P Strosznajder
Inflammatory processes and alterations of lipid metabolism play a crucial role in Alzheimer's disease (AD) and other neurodegenerative disorders. Polyunsaturated fatty acids (PUFA) metabolism impaired by cyclooxygenases (COX-1, COX-2), which are responsible for formation of several eicosanoids, and by lipoxygenases (LOXs) that catalyze the addition of oxygen to linolenic, arachidonic (AA), and docosahexaenoic acids (DHA) and other PUFA leading to formation of bioactive lipids, significantly affects the course of neurodegenerative diseases...
February 2016: Neurochemical Research
https://www.readbyqxmd.com/read/26427436/molecular-principles-for-decoding-homeostasis-disruptions-in-the-retinal-pigment-epithelium-significance-of-lipid-mediators-to-retinal-degenerative-diseases
#3
Nicolas G Bazan
Dysregulated neuroinflammatory signaling during impending disruption of homeostasis in retinal pigment epithelium (RPE) and photoreceptor cells (PRC) takes place in early stages of retinal degeneration. PRCs avidly retain and display the highest content in the human body of docosahexaenoic acid (DHA; an omega-3 essential fatty acid). Docosanoids are DHA-derived mediators, such as neuroprotectin D1 (NPD1), made on-demand that promote repair, phagocytic clearance, cell survival, and are active participants of effective, well-concerted homeostasis restoration...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/26047923/the-docosanoid-neuroprotectin-d1-induces-th-positive-neuronal-survival-in-a-cellular-model-of-parkinson-s-disease
#4
Jorgelina M Calandria, Michelle W Sharp, Nicolas G Bazan
Parkinson's disease (PD) does not manifest clinically until 80 % of striatal dopamine is reduced, thus most neuronal damage takes place before the patient presents clinical symptoms. Therefore, it is important to develop preventive strategies for this disease. In the experimental models of PD, 1-methyl-4-phenylpyridinium ion (MPP+) and rotenone induce toxicity in dopaminergic neurons. Neuroprotectin D1 (NPD1) displays neuroprotection in cells undergoing proteotoxic and oxidative stress. In the present report, we established an in vitro model using a primary neuronal culture from mesencephalic embryonic mouse tissue in which 17-20 % of neurons were TH-positive when differentiated in vitro...
November 2015: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/25633199/npd1-mediated-stereoselective-regulation-of-birc3-expression-through-crel-is-decisive-for-neural-cell-survival
#5
J M Calandria, A Asatryan, V Balaszczuk, E J Knott, B K Jun, P K Mukherjee, L Belayev, N G Bazan
Neuroprotectin D1 (NPD1), a docosahexaenoic acid (DHA)-derived mediator, induces cell survival in uncompensated oxidative stress (OS), neurodegenerations or ischemic stroke. The molecular principles underlying this protection remain unresolved. We report here that, in retinal pigment epithelial cells, NPD1 induces nuclear translocation and cREL synthesis that, in turn, mediates BIRC3 transcription. NPD1 activates NF-κB by an alternate route to canonical signaling, so the opposing effects of TNFR1 and NPD1 on BIRC3 expression are not due to interaction/s between NF-κB pathways...
August 2015: Cell Death and Differentiation
https://www.readbyqxmd.com/read/25617763/hippocampal-neuro-networks-and-dendritic-spine-perturbations-in-epileptogenesis-are-attenuated-by-neuroprotectin-d1
#6
Alberto E Musto, Chelsey P Walker, Nicos A Petasis, Nicolas G Bazan
PURPOSE: Limbic epileptogenesis triggers molecular and cellular events that foster the establishment of aberrant neuronal networks that, in turn, contribute to temporal lobe epilepsy (TLE). Here we have examined hippocampal neuronal network activities in the pilocarpine post-status epilepticus model of limbic epileptogenesis and asked whether or not the docosahexaenoic acid (DHA)-derived lipid mediator, neuroprotectin D1 (NPD1), modulates epileptogenesis. METHODS: Status epilepticus (SE) was induced by intraperitoneal administration of pilocarpine in adult male C57BL/6 mice...
2015: PloS One
https://www.readbyqxmd.com/read/25273880/neuroprotectin-protectin-d1-endogenous-biosynthesis-and-actions-on-diabetic-macrophages-in-promoting-wound-healing-and-innervation-impaired-by-diabetes
#7
Song Hong, Haibin Tian, Yan Lu, James Monroe Laborde, Filipe A Muhale, Quansheng Wang, Bhagwat V Alapure, Charles N Serhan, Nicolas G Bazan
Dysfunction of macrophages (MΦs) in diabetic wounds impairs the healing. MΦs produce anti-inflammatory and pro-resolving neuroprotectin/protectin D1 (NPD1/PD1, 10R,17S-dihydroxy-docosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid); however, little is known about endogenous NPD1 biosynthesis by MΦs and the actions of NPD1 on diabetic MΦ functions in diabetic wound healing. We used an excisional skin wound model of diabetic mice, MΦ depletion, MΦs isolated from diabetic mice, and mass spectrometry-based targeted lipidomics to study the time course progression of NPD1 levels in wounds, the roles of MΦs in NPD1 biosynthesis, and NPD1 action on diabetic MΦ inflammatory activities...
December 1, 2014: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/25212825/neuroprotectin-d1-is-synthesized-in-the-cone-photoreceptor-cell-line-661w-and-elicits-protection-against-light-induced-stress
#8
Y Kanan, W C Gordon, P K Mukherjee, N G Bazan, M R Al-Ubaidi
Docosahexaenoic acid (DHA), an omega-3 fatty acid family member, is obtained by diet or synthesized from dietary essential omega-3 linolenic acid and delivered systemically to the choriocapillaris, from where it is taken up by the retinal pigment epithelium (RPE). DHA is then transported to the inner segments of photoreceptors, where it is incorporated in phospholipids during the biogenesis of outer segment disk and plasma membranes. As apical photoreceptor disks are gradually shed and phagocytized by the RPE, DHA is retrieved and recycled back to photoreceptor inner segments for reassembly into new disks...
March 2015: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/25139562/protectins-and-maresins-new-pro-resolving-families-of-mediators-in-acute-inflammation-and-resolution-bioactive-metabolome
#9
REVIEW
Charles N Serhan, Jesmond Dalli, Romain A Colas, Jeremy W Winkler, Nan Chiang
Acute inflammatory responses are protective, yet without timely resolution can lead to chronic inflammation and organ fibrosis. A systems approach to investigate self-limited (self-resolving) inflammatory exudates in mice and structural elucidation uncovered novel resolution phase mediators in vivo that stimulate endogenous resolution mechanisms in inflammation. Resolving inflammatory exudates and human leukocytes utilize DHA and other n-3 EFA to produce three structurally distinct families of potent di- and trihydroxy-containing products, with several stereospecific potent mediators in each family...
April 2015: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/24972878/omega-3-polyunsaturated-fatty-acids-improve-mitochondrial-dysfunction-in-brain-aging-impact-of-bcl-2-and-npd-1-like-metabolites
#10
Sarah Afshordel, Stephanie Hagl, Deborah Werner, Nelli Röhner, Donat Kögel, Nicolas G Bazan, Gunter P Eckert
The present study investigated the effects of orally administered long chain omega-3 polyunsaturated fatty acids (PUFA) on mitochondrial function and processing of the amyloid precursor protein (APP) in brains of young (3 months old) and aged (24 months old) NMRI-mice. Neuroprotective properties of fish oil (FO) (1.6 ml/kg p.o.) were assessed ex vivo after 21 days in dissociated brain cells (DBC) and isolated mitochondria. Docosahexaenoic acid (DHA) levels were significantly lower in blood and brains of aged mice which were compensated by FO administration...
January 2015: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/24696140/identification-and-signature-profiles-for-pro-resolving-and-inflammatory-lipid-mediators-in-human-tissue
#11
Romain A Colas, Masakazu Shinohara, Jesmond Dalli, Nan Chiang, Charles N Serhan
Resolution of acute inflammation is an active process locally controlled by a novel genus of specialized pro-resolving mediators (SPM) that orchestrate key resolution responses. Hence, it is of general interest to identify individual bioactive mediators and profile their biosynthetic pathways with related isomers as well as their relation(s) to classic eicosanoids in mammalian tissues. Lipid mediator (LM)-SPM levels and signature profiles of their biosynthetic pathways were investigated using liquid chromatography-tandem mass spectrometry (LC-MS-MS)-based LM metabololipidomics...
July 1, 2014: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/24520010/a-versatile-and-stereocontrolled-total-synthesis-of-dihydroxylated-docosatrienes-containing-a-conjugated-e-e-z-triene
#12
Gandrath Dayaker, Thierry Durand, Laurence Balas
A versatile strategy featuring a Colvin rearrangement, hydrozirconation, a Sonogashira cross-coupling reaction and a Z-selective Wittig olefination, was successfully developed for the construction of a conjugated E,E,Z-triene subunit, flanked on both sides by two Z-allylic hydroxyl groups. This chemical pattern is found in many endogenous lipid metabolites such as maresin 1 (MaR1), neuroprotectin D1 (NPD1), and its aspirin triggered-isomer AT-NPD1, which not only counter-regulate inflammation but also actively orchestrate (at nanomolar doses) the resolution and termination program of acute inflammation while promoting wound healing, return to homeostasis and neuroprotection...
March 3, 2014: Chemistry: a European Journal
https://www.readbyqxmd.com/read/24307768/agonistic-approach-of-omega-3-omega-6-and-its-metabolites-with-bdnf-an-in-silico-study
#13
Yadla Phani Kumar, G Sri Shanmukha Srinivas, Yadu Mitravinda E, Lalitha Malla, Allam Appa Rao
Brain derived neurotrophic factor (BDNF) is a member of neurotrophic family of growth factors, mainly found in the hippocampus and cerebral cortex of brain. Studies have shown that there is a link between BDNF and cognitive dysfunction, as well as there is a relationship between the PUFAs intake and their effect on BDNF production. Intake of PUFAs, mainly omega-3 and omega-6 has show increase in production of BDNF in brain. In our study we performed docking studies on PUFAs and their metabolites with BDNF using MVD (Molegro Virtual Docker), this has shown that the metabolites of the PUFAs mainly LXA_4, NPD1, HDHA have shown more binding affinity towards BDNF...
2013: Bioinformation
https://www.readbyqxmd.com/read/24293102/regulation-of-neurotropic-signaling-by-the-inducible-nf-kb-sensitive-mirna-125b-in-alzheimer-s-disease-ad-and-in-primary-human-neuronal-glial-hng-cells
#14
REVIEW
Yuhai Zhao, Surjyadipta Bhattacharjee, Brandon M Jones, Jim Hill, Prerna Dua, Walter J Lukiw
Inducible microRNAs (miRNAs) perform critical regulatory roles in central nervous system (CNS) development, aging, health, and disease. Using miRNA arrays, RNA sequencing, enhanced Northern dot blot hybridization technologies, Western immunoblot, and bioinformatics analysis, we have studied miRNA abundance and complexity in Alzheimer's disease (AD) brain tissues compared to age-matched controls. In both short post-mortem AD and in stressed primary human neuronal-glial (HNG) cells, we observe a consistent up-regulation of several brain-enriched miRNAs that are under transcriptional control by the pro-inflammatory transcription factor NF-kB...
August 2014: Molecular Neurobiology
https://www.readbyqxmd.com/read/24262603/confusion-between-protectin-d1-pd1-and-its-isomer-protectin-dx-pdx-an-overview-on-the-dihydroxy-docosatrienes-described-to-date
#15
REVIEW
Laurence Balas, Michel Guichardant, Thierry Durand, Michel Lagarde
There is currently a growing interest in docosahexaenoic acid (DHA) oxygenated metabolites. Among them, protectin D1 (PD1), an endogenous dihydroxylated and non-cyclic docosatriene made through lipoxygenation and hydrolysis of an epoxide intermediate, shows appealing biological effects. However, with the present paper we wish to point out that results are sometimes assigned to PD1 while they are indeed related to its isomer protectin DX (PDX) made through double lipoxygenation only. These misleading conclusions urge us to review herein the structural/chemical and biological differences in the docosatrienes reported to date in the literature i...
April 2014: Biochimie
https://www.readbyqxmd.com/read/24107502/docosahexaenoic-acid-and-its-derivative-neuroprotectin-d1-display-neuroprotective-properties-in-the-retina-brain-and-central-nervous-system
#16
Nicolas G Bazan, Jorgelina M Calandria, William C Gordon
The significance of the selective enrichment in omega-3 essential fatty acids (docosahexaenoyl - DHA - chains of membrane phospholipids, 22C and 6 double bonds) in the nervous system (e.g. synaptic membranes and dendrites) has remained, until recently, incompletely understood. While studying mechanisms of neuronal survival, we contributed to the discovery of a docosanoid synthesized by 15-lipoxygenase-1 from DHA, which we dubbed neuroprotectin D1 (NPD1;10R,17S-dihydroxy-docosa-4Z,7Z,11E,13E,15E,19Z hexaenoic acid)...
2013: Nestlé Nutrition Institute Workshop Series
https://www.readbyqxmd.com/read/23981028/mediator-lipidomics-in-ophthalmology-targets-for-modulation-in-inflammation-neuroprotection-and-nerve-regeneration
#17
REVIEW
William C Gordon, Nicolas G Bazan
Studies in the central nervous system (CNS) and retina have revealed the significance of docosahexaenoic acid (DHA), an essential omega-3, 22 carbon 6 double bond (22:6), fatty acid. DHA is necessary for various functions in the CNS, including neuronal membrane bio- and synaptogenesis in memory and vision, and it is the precursor for docosanoids and neuroprotectin D1 (NPD1; 10R,17S-dihydroxy-docosa-4Z,7Z,11E,13E,15Z,19Z hexaenoic acid), a DHA bio-derivative with neuroprotective properties. This review covers three targets in ophthalmology for mediator lipidomics, a subgroup within the field of metabolomics: inflammation, neuroprotection and nerve regeneration...
October 2013: Current Eye Research
https://www.readbyqxmd.com/read/23942967/neuroprotectin-d1-reduces-the-severity-of-herpes-simplex-virus-induced-corneal-immunopathology
#18
Naveen K Rajasagi, Pradeep B J Reddy, Sachin Mulik, Per Gjorstrup, Barry T Rouse
PURPOSE: Neuroprotectin D1 (NPD1) is an anti-inflammatory and proresolving lipid mediator biosynthesized from the omega-3-polyunsaturated fatty acid docosahexaenoic acid (DHA). The purpose of this study is to test the therapeutic potential of NPD1 for the treatment of herpes simplex virus (HSV)-induced stromal keratitis (SK) using a mouse model. METHODS: C57BL/6 mice were infected ocularly with HSV-1 strain RE. Infected animals were treated topically with methyl ester prodrug NPD1 (300 ng/eye, 5-μL drop)...
2013: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/23922492/microglial-ramification-and-redistribution-concomitant-with-the-attenuation-of-choroidal-neovascularization-by-neuroprotectin-d1
#19
Kristopher G Sheets, Bokkyoo Jun, Yongdong Zhou, Min Zhu, Nicos A Petasis, William C Gordon, Nicolas G Bazan
PURPOSE: Neuroprotectin D1 (NPD1) attenuates laser-induced choroidal neovascularization (CNV) when administered intraperitoneally. Due to its lipophilicity and low molecular weight, NPD1 is well suited for topical delivery; thus, we investigated the efficacy of topically applied NPD1 in attenuating CNV. We also examined the effect of NPD1 on the recruitment and activation of microglia surrounding CNV lesions. METHODS: Mice were given laser-induced CNV and treated with NPD1 eye drops...
2013: Molecular Vision
https://www.readbyqxmd.com/read/23799606/neuroprotectin-d1-attenuates-brain-damage-induced-by-transient-middle-cerebral-artery-occlusion-in-rats-through-trpc6-creb-pathways
#20
Chengye Yao, Jiancheng Zhang, Fang Chen, Yun Lin
Neuroprotectin D1 (NPD1) may serve an endogenous neuroprotective role in brain ischemic injury, yet the underlying mechanism involved is poorly understood. In the present study, we aimed to investigate whether intracerebroventricular (ICV) injection of NPD1 is neuroprotective against transient focal cerebral ischemia. We also sought to verify the neuroprotective mechanisms of NPD1. Rats subjected to 2 h ischemia followed by reperfusion were treated with NPD1 at 2 h after reperfusion. PD98059 was administered 20 min prior to surgery...
August 2013: Molecular Medicine Reports
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