scholarly journals Maternal Dietary Docosahexaenoic Acid Alters Lipid Peroxidation Products and (n-3)/(n-6) Fatty Acid Balance in Offspring Mice

Metabolites ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 40 ◽  
Author(s):  
Bo Yang ◽  
Runting Li ◽  
Taeseon Woo ◽  
Jimmy Browning ◽  
Hailong Song ◽  
...  

The abundance of docosahexaenoic acid (DHA) in the mammalian brain has generated substantial interest in the search for its roles in regulating brain functions. Our recent study with a gene/stress mouse model provided evidence to support the ability for the maternal supplement of DHA to alleviate autism-associated behavior in the offspring. DHA and arachidonic acid (ARA) are substrates of enzymatic and non-enzymatic reactions, and lipid peroxidation results in the production of 4-hydroxyhexenal (4-HHE) and 4-hydroxynonenal (4-HNE), respectively. In this study, we examine whether a maternal DHA-supplemented diet alters fatty acids (FAs), as well as lipid peroxidation products in the pup brain, heart and plasma by a targeted metabolite approach. Pups in the maternal DHA-supplemented diet group showed an increase in DHA and a concomitant decrease in ARA in all brain regions examined. However, significant increases in 4-HHE, and not 4-HNE, were found mainly in the cerebral cortex and hippocampus. Analysis of heart and plasma showed large increases in DHA and 4-HHE, but a significant decrease in 4-HNE levels only in plasma. Taken together, the DHA-supplemented maternal diet alters the (n-3)/(n-6) FA ratio, and increases 4-HHE levels in pup brain, heart and plasma. These effects may contribute to the beneficial effects of DHA on neurodevelopment, as well as functional changes in other body organs.

2019 ◽  
Vol 20 (4) ◽  
pp. 932 ◽  
Author(s):  
Grace Sun ◽  
Runting Li ◽  
Bo Yang ◽  
Kevin Fritsche ◽  
David Beversdorf ◽  
...  

High levels of docosahexaenoic acid (DHA) in the phospholipids of mammalian brain have generated increasing interest in the search for its role in regulating brain functions. Recent studies have provided evidence for enhanced protective effects when DHA is administered in combination with phytochemicals, such as quercetin. DHA and quercetin can individually suppress lipopolysaccharide (LPS)–induced oxidative/inflammatory responses and enhance the antioxidative stress pathway involving nuclear factor erythroid-2 related factor 2 (Nrf2). However, studies with BV-2 microglial cells indicated rather high concentrations of DHA (IC50 in the range of 60–80 µM) were needed to produce protective effects. To determine whether quercetin combined with DHA can lower the levels of DHA needed to produce protective effects in these cells is the goal for this study. Results showed that low concentrations of quercetin (2.5 µM), in combination with DHA (10 µM), could more effectively enhance the expression of Nrf2 and heme oxygenase 1 (HO-1), and suppress LPS–induced nitric oxide, tumor necrosis factor-α, phospho-cytosolic phospholipase A2, reactive oxygen species, and 4-hydroxynonenal, as compared to the same levels of DHA or quercetin alone. These results provide evidence for the beneficial effects of quercetin in combination with DHA, and further suggest their potential as nutraceuticals for improving health.


Author(s):  
Vincent R. Daria ◽  
Michael Lawrence Castañares ◽  
Hans-A. Bachor

AbstractThe challenge to understand the complex neuronal circuit functions in the mammalian brain has brought about a revolution in light-based neurotechnologies and optogenetic tools. However, while recent seminal works have shown excellent insights on the processing of basic functions such as sensory perception, memory, and navigation, understanding more complex brain functions is still unattainable with current technologies. We are just scratching the surface, both literally and figuratively. Yet, the path towards fully understanding the brain is not totally uncertain. Recent rapid technological advancements have allowed us to analyze the processing of signals within dendritic arborizations of single neurons and within neuronal circuits. Understanding the circuit dynamics in the brain requires a good appreciation of the spatial and temporal properties of neuronal activity. Here, we assess the spatio-temporal parameters of neuronal responses and match them with suitable light-based neurotechnologies as well as photochemical and optogenetic tools. We focus on the spatial range that includes dendrites and certain brain regions (e.g., cortex and hippocampus) that constitute neuronal circuits. We also review some temporal characteristics of some proteins and ion channels responsible for certain neuronal functions. With the aid of the photochemical and optogenetic markers, we can use light to visualize the circuit dynamics of a functioning brain. The challenge to understand how the brain works continue to excite scientists as research questions begin to link macroscopic and microscopic units of brain circuits.


2021 ◽  
Author(s):  
◽  
Michael Kwame Appenteng

Cyanogenic glycosides (CNGs) are naturally occurring plant molecules (nitrogenous plant secondary metabolites) which consist of an aglycone and a sugar moiety. Hydrogen cyanide (HCN) is released from these compounds following enzymatic hydrolysis causing potential toxicity issues. The presence of CNGs in American elderberry (AE) fruit, Sambucus nigra (subsp. canadensis), is uncertain. A sensitive, reproducible and robust LC-MS/MS method was developed and optimized for accurate identification and quantification of the intact glycoside. A complimentary picrate paper test method was modified to determine the total cyanogenic potential (TCP). TCP analysis was performed using a camera-phone and UV-Vis spectrophotometry. A method validation was conducted, and the developed methods were successfully applied to the assessment of TCP and quantification of intact CNGs in different tissues of AE samples. Results showed no quantifiable trace of CNGs in commercial AE juice. Levels of CNGs found in various fruit tissues of AE cultivars studied ranged from between 0.12-6.38 [micro-gram]/g. In pressed juice samples, the concentration range measured was 0.29-2.36 [micro-gram]/mL and in seeds the amounts was 0.12-2.38 [micro-gram]/g. TCP was highest in the stems and green berries. CNG levels in all tissues were generally low and at a level that poses no threat to consumers of fresh and processed AE products. The abundance of docosahexaenoic acid (DHA) in phospholipids in the brain and retina has generated interest to search for its role in mediating neurological functions. Besides the source of many oxylipins with pro-resolving properties, DHA also undergoes peroxidation, producing 4-hydroxyhexenal (4-HHE), although its function remains elusive. Despite wide dietary consumption, whether supplementation of DHA may alter the peroxidation products and their relationship to phospholipid species in brain and other body organs have not been explored sufficiently. In this study, adult mice were administered a control or DHA-enriched diet for three weeks, and phospholipid species and peroxidation products were examined in brain, heart and plasma. Results demonstrated that this dietary regimen increased (n-3) and decreased (n-6) species to different extent in all major phospholipid classes (PC, dPE, PE-pl, PI and PS) examined. Besides changes in phospholipid species, DHA-enriched diet also showed substantial increases in 4-HHE in brain, heart and plasma. Among different brain regions, the hippocampus responded to the DHA-enriched diet showing significant increase in 4-HHE. Considering the pro- and anti-inflammatory pathways mediated by the (n-6) and (n-3) polyunsaturated fatty acids, unveiling the ability for DHA-enriched diet to alter phospholipid species and lipid peroxidation products in the brain and in different body organs may be an important step forward towards understanding the mechanism(s) for this (n-3) fatty acid on health and diseases. Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted social communication and repetitive behaviors. Prenatal stress is critical in neurodevelopment and increases risk for ASD, particularly in those with greater genetic susceptibility to stress. Docosahexaenoic acid (DHA) is one of the most abundant [omega]-3 fatty acids in mammalian brain, and dietary [omega]-3 fatty acid affects the development and maintenance of brain structure. We investigated whether prenatal supplementation of DHA alleviates autistic-like behaviors in a gene/stress mouse model and how it alters lipid peroxidation activity in the brain. Pregnant heterozygous serotonin transporter knockout (SERT-KO) and wild-type (WT) dams were placed in either non-stressed control conditions or chronic variable stress conditions and fed either a control diet or a DHA-rich (1 [percent] by wt) diet. Offspring of each group were assessed for anxiety and autism-associated behavior at post-natal day 60, including an open field test, elevatedplus maze test, repetitive behavior, and the 3-chamber social approach test. Our LC-MS-based method was used to follow changes in peroxidation product concentrations in mouse plasma, heart, and cerebral cortex.


Blood ◽  
2003 ◽  
Vol 101 (12) ◽  
pp. 4990-4997 ◽  
Author(s):  
Sanda Sturlan ◽  
Melanie Baumgartner ◽  
Erich Roth ◽  
Thomas Bachleitner-Hofmann

AbstractRecent reports indicate a broad spectrum of antileukemic activity for arsenic trioxide (As2O3) due to its ability to induce apoptosis via intracellular production of reactive oxygen species (ROS). Despite its potent apoptotic mechanism, As2O3 is not equally effective in all leukemic cells, which has prompted a search for agents enhancing As2O3 efficacy. Recently, evidence has been gathered that the polyunsaturated fatty acid docosahexaenoic acid (DHA) may sensitize tumor cells to ROS-inducing anticancer agents. The aim of our investigation was to evaluate whether DHA enhances As2O3-mediated apoptosis in As2O3-resistant HL-60 cells. While 1 μM As2O3 or 25 μM DHA reduced cell viability to 85.8% ± 2.9% and 69.2% ± 3.6%, combined treatment with As2O3 and DHA reduced viability to 13.0% ± 9.9% with a concomitant increase of apoptosis. Apoptotic cell death was preceded by collapse of the mitochondrial membrane potential, increased expression of proapoptotic B-cell lymphoma protein-2–associated X protein (Bax), and caspase-3 activation. Importantly, the combined effect of As2O3 and DHA was associated with increased production of intracellular ROS and toxic lipid peroxidation products and was abolished by the antioxidant vitamin E or when oleic acid (a nonperoxidizable fatty acid) was used in place of DHA. Intracellular ROS and toxic lipid peroxidation products most likely constitute the key mediators contributing to the combined effect of As2O3 and DHA. Our data provide the first evidence that DHA may help to extend the therapeutic spectrum of As2O3 and suggest that the combination of As2O3 and DHA could be more broadly applied in leukemia therapy.


2020 ◽  
Vol 117 (46) ◽  
pp. 28743-28753 ◽  
Author(s):  
Jua Lee ◽  
Seungshin Ha ◽  
Minsoo Kim ◽  
Seong-Wook Kim ◽  
Jaekyung Yun ◽  
...  

Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale “omics” studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties. Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development. We observed an apparent diversity in the glycome expression patterns, which is spatially well-preserved among nine different brain regions in mouse. Next, we explored whether the glycome expression pattern changes temporally during postnatal brain development by examining the prefrontal cortex (PFC) at different time point across six postnatal stages in mouse. We found that glycan expression profiles were dynamically regulated during postnatal developments. A similar result was obtained in PFC samples from humans ranging in age from 39 d to 49 y. Novel glycans unique to the brain were also identified. Interestingly, changes primarily attributed to sialylated and fucosylated glycans were extensively observed during PFC development. Finally, based on the vast heterogeneity of glycans, we constructed a core glyco-synthesis map to delineate the glycosylation pathway responsible for the glycan diversity during the PFC development. Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.


2015 ◽  
Vol 16 (1-2) ◽  
pp. 44-54 ◽  
Author(s):  
Marcus O.W. Grimm ◽  
Viola J. Haupenthal ◽  
Janine Mett ◽  
Christoph P. Stahlmann ◽  
Tamara Blümel ◽  
...  

Author(s):  
Sarah F. Beul ◽  
Alexandros Goulas ◽  
Claus C. Hilgetag

AbstractStructural connections between cortical areas form an intricate network with a high degree of specificity. Many aspects of this complex network organization in the adult mammalian cortex are captured by an architectonic type principle, which relates structural connections to the architectonic differentiation of brain regions. In particular, the laminar patterns of projection origins are a prominent feature of structural connections that varies in a graded manner with the relative architectonic differentiation of connected areas in the adult brain. Here we show that the architectonic type principle is already apparent for the laminar origins of cortico-cortical projections in the immature cortex of the macaque monkey. We find that prenatal and neonatal laminar patterns correlate with cortical architectonic differentiation, and that the relation of laminar patterns to architectonic differences between connected areas is not substantially altered by the complete loss of visual input. Moreover, we find that the degree of change in laminar patterns that projections undergo during development varies in proportion to the relative architectonic differentiation of the connected areas. Hence, it appears that initial biases in laminar projection patterns become progressively strengthened by later developmental processes. These findings suggest that early neurogenetic processes during the formation of the brain are sufficient to establish the characteristic laminar projection patterns. This conclusion is in line with previously suggested mechanistic explanations underlying the emergence of the architectonic type principle and provides further constraints for exploring the fundamental factors that shape structural connectivity in the mammalian brain.


2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 293-294
Author(s):  
Murat Baymishev ◽  
Sergey Eremin ◽  
Kirill Plemyashov ◽  
Khamidulla Baymishev ◽  
Igor Konopel’tsev ◽  
...  

Abstract The aim of the study was to determine the etiopathogenesis of reproductive dysfunction in highly productive cows. Studies were conducted on cows of black-motley breed, aged 3–5 lactations, with a live weight of 480–520 kg. Cows were divided into two groups. The first group included 20 cows effective inseminated after the first insemination. The second group included 17 cows that did not fertilize after the first insemination. Blood samples (n = 253) were taken from 4–7; 14–17; 24–34; 35–50; 88–95; 195–210 days of pregnancy; during the beginning of dry period (DP); 1–4 days before calving and on the first day after calving. The content of total serum lipids in pregnant animals was 15.8% higher compared to unfertilized animals. In non-pregnant cows, a decrease in free cholesterol (by 28.65%), especially in its ether-bound fraction (14.91%), indicates a lower synthetic function of the liver, which is confirmed by the low serum levels of vitamins A and E (a difference of 11.3 and 23.65%). The DP was characterized by a significant increase in the products of lipid peroxidation - malondialdehyde by 12–17%, diene and triene conjugates - by 10–15 and 8–15%, respectively, and 1–4 days before calving in cows, which subsequently had a pathological calving, in particular - retention of placenta (5 cows), were characterized by an increased content in the blood plasma of lipid peroxidation products. Thus, the difference in the number of dienes, trienes, and malondialdehyde products was 14.0, 12.0, and 23.5%, compared with animals without obstetric pathology. On the first day after calving, this difference increased even more. Cows with retention of placenta had a significantly higher level of lipid peroxidation products and were characterized by a predominance of oxidized products over the antiradical thiol disulfide and ascorbate systems restored in the antioxidant balance.


Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 240
Author(s):  
Kyoko Hasebe ◽  
Michael D. Kendig ◽  
Margaret J. Morris

The widespread consumption of ‘western’-style diets along with sedentary lifestyles has led to a global epidemic of obesity. Epidemiological, clinical and preclinical evidence suggests that maternal obesity, overnutrition and unhealthy dietary patterns programs have lasting adverse effects on the physical and mental health of offspring. We review currently available preclinical and clinical evidence and summarise possible underlying neurobiological mechanisms by which maternal overnutrition may perturb offspring cognitive function, affective state and psychosocial behaviour, with a focus on (1) neuroinflammation; (2) disrupted neuronal circuities and connectivity; and (3) dysregulated brain hormones. We briefly summarise research implicating the gut microbiota in maternal obesity-induced changes to offspring behaviour. In animal models, maternal obesogenic diet consumption disrupts CNS homeostasis in offspring, which is critical for healthy neurodevelopment, by altering hypothalamic and hippocampal development and recruitment of glial cells, which subsequently dysregulates dopaminergic and serotonergic systems. The adverse effects of maternal obesogenic diets are also conferred through changes to hormones including leptin, insulin and oxytocin which interact with these brain regions and neuronal circuits. Furthermore, accumulating evidence suggests that the gut microbiome may directly and indirectly contribute to these maternal diet effects in both human and animal studies. As the specific pathways shaping abnormal behaviour in offspring in the context of maternal obesogenic diet exposure remain unknown, further investigations are needed to address this knowledge gap. Use of animal models permits investigation of changes in neuroinflammation, neurotransmitter activity and hormones across global brain network and sex differences, which could be directly and indirectly modulated by the gut microbiome.


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