scholarly journals The Effects of Doxorubicin-based Chemotherapy and Omega-3 Supplementation on Mouse Brain Lipids

Metabolites ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 208
Author(s):  
Djawed Bennouna ◽  
Melissa Solano ◽  
Tonya S. Orchard ◽  
A. Courtney DeVries ◽  
Maryam Lustberg ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Breast Cancer Survivors ◽  
Omega 3 ◽  
Resolvin D1 ◽  
Brain Lipids ◽  
Fatty Acid Supplementation ◽  
Ovariectomized Mice ◽  
The Brain ◽  
Injection Study

Chemotherapy-induced cognitive impairment affects ~30% of breast cancer survivors, but the effects on how chemotherapy impacts brain lipids, and how omega-3 polyunsaturated fatty acid supplementation may confer protection, is unknown. Ovariectomized mice were randomized to two rounds of injections of doxorubicin + cyclophosphamide or vehicle after consuming a diet supplemented with 2% or 0% EPA+DHA, and sacrificed 4, 7, and 14 days after the last injection (study 1, n = 120) or sacrificed 10 days after the last injection (study 2, n = 40). Study 1 whole brain samples were extracted and analyzed by UHPLC-MS/MS to quantify specialized pro-resolving mediators (SPMs). Lipidomics analyses were performed on hippocampal extracts from study 2 to determine changes in the brain lipidome. Study 1 results: only resolvin D1 was present in all samples, but no differences in concentration were observed (P > 0.05). Study 2 results: chemotherapy was positively correlated with omega-9 fatty acids, and EPA+DHA supplementation helped to maintain levels of plasmalogens. No statistically significant chemotherapy*diet effect was observed. Results demonstrate a limited role of SPMs in the brain post-chemotherapy, but a significant alteration of hippocampal lipids previously associated with other models of cognitive impairment (i.e., Alzheimer’s and Parkinson’s disease).

scholarly journals The Influence of Omega-3 Fatty Acid Supplementation on the Brain Lipidome After Chemotherapy (P15-024-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Melissa Solano ◽  
Djawed Bennouna ◽  
Tonya Orchard ◽  
A Courtney DeVries ◽  
Rachel Kopec
Keyword(s):  
Fatty Acid ◽  
Dietary Group ◽  
Omega 3 ◽  
Brain Lipids ◽  
Fatty Acid Supplementation ◽  
Acid Supplementation ◽  
Omega 3 Fatty Acid ◽  
Ovariectomized Mice ◽  
Maresin 1 ◽  
The Brain

Abstract Objectives Solid tumor chemotherapy produces long-term cognitive side effects well beyond treatment, but the structural changes on brain chemistry are unknown. A diet supplemented with omega-3 fatty acids (EPA + DHA) before and during chemotherapy partially protects the cerebral tissue against some of the chemo-induced modifications. We hypothesize that EPA + DHA supplementation results in a greater neuroinflammation-resolving response mediated by specialized pro-resolving mediators (SPMs i.e., omega-3 derived metabolites which attenuate inflammation), and reduces oxidation of structural brain lipids. Methods For four weeks, ovariectomized mice were fed a 2% kcal EPA + DHA supplemented (n = 60) or control diet (n = 60), followed by two treatments with vehicle (n = 30 per dietary group) or doxorubicin (n = 30 per dietary group). Animals were sacrificed at 4, 7, and 14 days post-treatment, and samples extracted and purified with SPE. Targeted analyses (LC-MS/MS) were performed on extracts, using stable isotope internal standards for SPM quantitation (i.e., resolvin E1, D1, D2, D3, D5, maresin 1, protectin D1). Untargeted LC-HRMS metabolomics analyses were performed on the hippocampal extracts of follow-up set of animals, to determine changes in the brain lipidome. Results Resolvin D1 was quantifiable in all samples regardless of dietary or treatment group, and correlations were observed with orthogonal measures of inflammation in chemo-treated animals. Resolvin D3, maresin 1, and protectin D1 were detected in a subset of animals. A cluster of lipid-based metabolites differentiated animals receiving chemotherapy with omega-3 fatty acid supplementation from those not receiving the supplementation. Conclusions The protective effects of EPA + DHA supplementation on chemo-induced cerebral damage appear to be only partially correlated with SPM synthesis over the time course observed. Funding Sources This research was supported by an OSU Foods for Health Discovery Themes Initiative SEEDS grant. The mouse samples were collected under NIH R01CA189947. The sample analyses were partially supported by NIH Award Number Grant P30 CA016058, OSU, and OSUCCC.

Lipidomics and cognitive dysfunction – A Narrative review

2020 ◽  
Vol 45 (2) ◽  
Author(s):  
Arpita Chakraborty ◽  
Samir Kumar Praharaj ◽  
R. V. Krishnananda Prabhu ◽  
M. Mukhyaprana Prabhu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Vascular Dementia ◽  
Cognitive Dysfunction ◽  
Neurological Disorders ◽  
Brain Lipids ◽  
Complex Lipids ◽  
Functional Components ◽  
The Brain

AbstractBackgroundMore than half portion of the brain is formed by lipids. They play critical roles in maintaining the brain's structural and functional components. Any dysregulation in these brain lipids can lead to cognitive dysfunction which are associated with neurological disorders such as Alzheimer's disease, Parkinson's disease, schizophrenia, vascular dementia etc. Studies have linked lipids with cognitive impairment. But not much has been studied about the complex brain lipids which might play a pivotal role in cognitive impairment. This review aims to highlight the lipidomic profiles in patients with cognitive dysfunction.ResultsForty-five articles were reviewed. These studies show alterations in complex lipids such as sphingolipids, phospholipids, glycolipids and sterols in brain in various neurological disorders such as vascular dementia, Parkinson's and Alzheimer's disease. However, the classes of fatty acids in these lipids involved are different across studies.ConclusionsThere is a need for targeted lipidomics analysis, specifically including sphingolipids in patients with neurodegenerative disorders so as to improve diagnostics as well as management of these disorders.

Abnormalities of the HPA axis in affective disorders: clinical subtypes and potential treatments

2006 ◽  
Vol 18 (5) ◽  
pp. 193-209 ◽  
Author(s):  
Richard J. Porter ◽  
Peter Gallagher
Keyword(s):  
Bipolar Disorder ◽  
Cognitive Impairment ◽  
Hpa Axis ◽  
Affective Disorders ◽  
Psychotic Depression ◽  
Review Of The Literature ◽  
Hpa Axis Dysregulation ◽  
New Evidence ◽  
The Brain

Background:New evidence is emerging regarding abnormalities of hypothalamic-pituitary-adrenal (HPA) axis function in subtypes of affective disorders. Adverse effects of HPA axis dysregulation may include dysfunction of monoaminergic transmitter systems, cognitive impairment and peripheral effects. Newer treatments specifically targeting the HPA axis are being developed.Objective:To review these developments focusing particularly on the glucocorticoid receptor (GR) antagonist mifepristone.Method:A selective review of the literature.Results:The function of GRs is increasingly being defined. The role of corticotrophin-releasing hormone (CRH) and dehydroepiandrosterone (DHEA) in the brain is also increasingly understood. HPA axis function is particularly likely to be abnormal in psychotic depression and bipolar disorder, and it is in these conditions that trials of the GR antagonist mifepristone are being focused. CRH antagonists and DHEA are also being investigated as potential treatments.Conclusion:Initial studies of mifepristone and other HPA-axis-targeting agents in psychotic depression and bipolar disorder are encouraging and confirmatory studies are awaited.

scholarly journals Role of the glymphatic system in ageing and diabetes mellitus impaired cognitive function

2019 ◽  
Vol 4 (2) ◽  
pp. 90-92 ◽  
Author(s):  
Li Zhang ◽  
Michael Chopp ◽  
Quan Jiang ◽  
Zhenggang Zhang
Keyword(s):  
Diabetes Mellitus ◽  
Cognitive Impairment ◽  
Interstitial Fluid ◽  
Amyloid Β ◽  
Brain Parenchyma ◽  
Glymphatic System ◽  
Impaired Cognitive Function ◽  
Increased Risk ◽  
The Brain

Diabetes mellitus (DM) is a common metabolic disease in the middle-aged and older population, and is associated with cognitive impairment and an increased risk of developing dementia. The glymphatic system is a recently characterised brain-wide cerebrospinal fluid and interstitial fluid drainage pathway that enables the clearance of interstitial metabolic waste from the brain parenchyma. Emerging data suggest that DM and ageing impair the glymphatic system, leading to accumulation of metabolic wastes including amyloid-β within the brain parenchyma, and consequently provoking cognitive dysfunction. In this review, we concisely discuss recent findings regarding the role of the glymphatic system in DM and ageing associated cognitive impairment.

Targeting the effects of omega-3 and omega-6 fatty acid supplementation on schizophrenic spectrum disorders: Role of neuroimaging

2007 ◽  
Vol 69 (2) ◽  
pp. 466-467 ◽  
Author(s):  
M. Sota ◽  
C. Allegri ◽  
M. Cortesi ◽  
F. Barale ◽  
P. Politi ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Omega 3 ◽  
Fatty Acid Supplementation ◽  
Acid Supplementation ◽  
Omega 6 ◽  
Spectrum Disorders

scholarly journals Role of Omega-3 Fatty Acid Supplementation in Inflammation and Malignancy

2004 ◽  
Vol 3 (2) ◽  
pp. 98-111 ◽  
Author(s):  
David H. Jho ◽  
Shawn M. Cole ◽  
Ellyn M. Lee ◽  
N. Joseph Espat
Keyword(s):  
Fatty Acid ◽  
Omega 3 ◽  
Fatty Acid Supplementation ◽  
Acid Supplementation ◽  
Omega 3 Fatty Acid

scholarly journals Rewiring of the Serotonin System in Major Depression

2021 ◽  
Vol 12 ◽  
Author(s):  
Faranak Vahid-Ansari ◽  
Paul R. Albert
Keyword(s):  
Mental Illness ◽  
Cognitive Impairment ◽  
Major Depression ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Chronic Treatment ◽  
Brain Regions ◽  
Synaptic Organization ◽  
Serotonin System ◽  
The Brain

Serotonin is a key neurotransmitter that is implicated in a wide variety of behavioral and cognitive phenotypes. Originating in the raphe nuclei, 5-HT neurons project widely to innervate many brain regions implicated in the functions. During the development of the brain, as serotonin axons project and innervate brain regions, there is evidence that 5-HT plays key roles in wiring the developing brain, both by modulating 5-HT innervation and by influencing synaptic organization within corticolimbic structures. These actions are mediated by 14 different 5-HT receptors, with region- and cell-specific patterns of expression. More recently, the role of the 5-HT system in synaptic re-organization during adulthood has been suggested. The 5-HT neurons have the unusual capacity to regrow and reinnervate brain regions following insults such as brain injury, chronic stress, or altered development that result in disconnection of the 5-HT system and often cause depression, anxiety, and cognitive impairment. Chronic treatment with antidepressants that amplify 5-HT action, such as selective serotonin reuptake inhibitors (SSRIs), appears to accelerate the rewiring of the 5-HT system by mechanisms that may be critical to the behavioral and cognitive improvements induced in these models. In this review, we survey the possible 5-HT receptor mechanisms that could mediate 5-HT rewiring and assess the evidence that 5-HT-mediated brain rewiring is impacting recovery from mental illness. By amplifying 5-HT-induced rewiring processes using SSRIs and selective 5-HT agonists, more rapid and effective treatments for injury-induced mental illness or cognitive impairment may be achieved.

scholarly journals Role of OMEGA-3 Fatty Acid Supplementation in COVID-19 Patients: A Narrative Review

2021 ◽  
Vol 04 (02) ◽  
Author(s):  
Zoia Akram ◽  
Alekhya Allenki ◽  
Sindhu Kishore ◽  
Dolly Ogwu ◽  
Olufunlola Titilayo Adefalu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Narrative Review ◽  
Omega 3 ◽  
Fatty Acid Supplementation ◽  
Acid Supplementation ◽  
Omega 3 Fatty Acid

scholarly journals Role of age-related alterations of the cerebral venous circulation in the pathogenesis of vascular cognitive impairment

2019 ◽  
Vol 316 (5) ◽  
pp. H1124-H1140 ◽  
Author(s):  
Gabor A. Fulop ◽  
Stefano Tarantini ◽  
Andriy Yabluchanskiy ◽  
Andrea Molnar ◽  
Calin I. Prodan ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cerebral Arteries ◽  
Vascular Cognitive Impairment ◽  
Cerebral Veins ◽  
Older Individuals ◽  
Low Velocity ◽  
Venous Circulation ◽  
Age Related ◽  
The Brain

There has been an increasing appreciation of the role of vascular contributions to cognitive impairment and dementia (VCID) associated with old age. Strong preclinical and translational evidence links age-related dysfunction and structural alterations of the cerebral arteries, arterioles, and capillaries to the pathogenesis of many types of dementia in the elderly, including Alzheimer’s disease. The low-pressure, low-velocity, and large-volume venous circulation of the brain also plays critical roles in the maintenance of homeostasis in the central nervous system. Despite its physiological importance, the role of age-related alterations of the brain venous circulation in the pathogenesis of vascular cognitive impairment and dementia is much less understood. This overview discusses the role of cerebral veins in the pathogenesis of VCID. Pathophysiological consequences of age-related dysregulation of the cerebral venous circulation are explored, including blood-brain barrier disruption, neuroinflammation, exacerbation of neurodegeneration, development of cerebral microhemorrhages of venous origin, altered production of cerebrospinal fluid, impaired function of the glymphatics system, dysregulation of cerebral blood flow, and ischemic neuronal dysfunction and damage. Understanding the age-related functional and phenotypic alterations of the cerebral venous circulation is critical for developing new preventive, diagnostic, and therapeutic approaches to preserve brain health in older individuals.

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