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Linlin Zhang, Niccolò Terrando, Zhen-Zhong Xu, Sangsu Bang, Sven-Eric Jordt, William Maixner, Charles N Serhan, Ru-Rong Ji
Mechanisms of pain resolution are largely unclear. Increasing evidence suggests that specialized pro-resolving mediators (SPMs), derived from fish oil docosahexaenoic acid (DHA), promote the resolution of acute inflammation and potently inhibit inflammatory and neuropathic pain. In this study, we examined the analgesic impact of DHA and DHA-derived SPMs in a mouse model of post-operative pain induced by tibial bone fracture (fPOP). Intravenous perioperative treatment with DHA (500 μg), resolvin D1 (RvD1, 500 ng) and maresin 1 (MaR1, 500 ng), 10 min and 24 h after the surgery, delayed the development of fPOP (mechanical allodynia and cold allodynia)...
2018: Frontiers in Pharmacology
Lynn Calvin Shaw, Sergio Li Calzi, Nan Li, Leni Moldovan, Nilanjana Sengupta-Caballero, Judith Lindsey Quigley, Mircea Ivan, Bokkyoo Jun, Nicolas G Bazan, Michael Edwin Boulton, Julia Busik, Josef Neu, Maria B Grant
Purpose: Low levels of the long chain polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA) have been implicated in retinopathy of prematurity (ROP). However, oral DHA suffers from poor palatability and is associated with increased bleeding in premature infants. We asked whether oral administration of the neutraceutical arginine-glutamine (Arg-Glu) could increase retinal DHA and improve outcomes in a mouse model of oxygen-induced retinopathy (OIR). Methods: Postnatal day 7 (P7) pups were maintained at 75% oxygen for 5 days and then returned to room air on P12...
February 1, 2018: Investigative Ophthalmology & Visual Science
Eric J Knott, William C Gordon, Bokkyoo Jun, Khanh Do, Nicolas G Bazan
Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are necessary for functional cell integrity. Preconditioning (PC), as we define it, is an acquired protection or resilience by a cell, tissue, or organ to a lethal stimulus enabled by a previous sublethal stressor or stimulus. In this study, we provide evidence that the omega-3 fatty acid docosahexaenoic acid (DHA) and its derivatives, the docosanoids 17-hydroxy docosahexaenoic acid (17-HDHA) and neuroprotectin D1 (NPD1), facilitate cell survival in both in vitro and in vivo models of retinal PC...
November 24, 2017: Cellular and Molecular Neurobiology
Aram Asatryan, Nicolas G Bazan
Docosahexaenoic acid, enriched in the brain and retina, generates docosanoids in response to disruptions of cellular homeostasis. Docosanoids include neuroprotectin D1 (NPD1), which is decreased in the CA1 hippocampal area of patients with early-stage Alzheimer's disease (AD). We summarize here how NPD1 elicits neuroprotection by up-regulating c-REL, a nuclear factor (NF)-κB subtype that, in turn, enhances expression of BIRC3 (baculoviral inhibitor of apoptosis repeat-containing protein 3) in the retina and in experimental stroke, leading to neuroprotection...
July 28, 2017: Journal of Biological Chemistry
Ludmila Belayev, Pranab K Mukherjee, Veronica Balaszczuk, Jorgelina M Calandria, Andre Obenaus, Larissa Khoutorova, Sung-Ha Hong, Nicolas G Bazan
Ring finger protein 146 (Iduna) facilitates DNA repair and protects against cell death induced by NMDA receptor-mediated glutamate excitotoxicity or by cerebral ischemia. Neuroprotectin D1 (NPD1), a docosahexaenoic acid (DHA)-derived lipid mediator, promotes cell survival under uncompensated oxidative stress (UOS). Our data demonstrate that NPD1 potently upregulates Iduna expression and provides remarkable cell protection against UOS. Iduna, which was increased by the lipid mediator, requires the presence of the poly(ADP-ribose) (PAR) sites...
June 2017: Cell Death and Differentiation
Rémy Bosviel, Laurie Joumard-Cubizolles, Giulia Chinetti-Gbaguidi, Dominique Bayle, Corinne Copin, Nathalie Hennuyer, Isabelle Duplan, Bart Staels, Giuseppe Zanoni, Alessio Porta, Laurence Balas, Jean-Marie Galano, Camille Oger, Andrzej Mazur, Thierry Durand, Cécile Gladine
Whereas the anti-inflammatory properties and mechanisms of action of long chain ω3 PUFAs have been abundantly investigated, research gaps remain regarding the respective contribution and mechanisms of action of their oxygenated metabolites collectively known as oxylipins. We conducted a dose-dependent and comparative study in human primary macrophages aiming to compare the anti-inflammatory activity of two types of DHA-derived oxylipins including the well-described protectins (NPD1 and PDX), formed through lipoxygenase pathway and the neuroprostanes (14-A4t - and 4-F4t -NeuroP) formed through free-radical mediated oxygenation and expected to be new anti-inflammatory mediators...
February 2017: Free Radical Biology & Medicine
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...
July 2017: Molecular Neurobiology
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
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
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
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
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
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
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
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
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
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
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
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
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
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