Dietary Long‐Chain n‐3 Polyunsaturated Fatty Acid Supplementation Alters Electrophysiological Properties in the Nucleus Accumbens and Emotional Behavior in Naïve and Chronically Stressed Mice

Long‐chain (LC) n‐3 polyunsaturated fatty acids (PUFAs) have drawn attention in the field of neuropsychiatric disorders, in particular depression. However, whether dietary supplementation with LC n‐3 PUFA protects from the development of mood disorders is still a matter of de-bate. In the present study, we studied the effect of a two‐month exposure to isocaloric diets containing n‐3 PUFAs in the form of relatively short‐chain (SC) (6% of rapeseed oil, enriched in α‐linolenic acid (ALA)) or LC (6% of tuna oil, enriched in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) PUFAs on behavior and synaptic plasticity of mice submitted or not to a chronic social defeat stress (CSDS), previously reported to alter emotional and social behavior, as well as synaptic plasticity in the nucleus accumbens (NAc). First, fatty acid content and lipid metabolism gene expression were measured in the NAc of mice fed a SC (control) or LC n‐3 (supplemented) PUFA diet. Our results indicate that LC n‐3 supplementation significantly increased some n‐3 PUFAs, while decreasing some n‐6 PUFAs. Then, in another cohort, control and n‐3 PUFA‐supplemented mice were subjected to CSDS, and social and emotional behaviors were assessed, together with long‐term depression plasticity in accumbal medium spiny neurons. Overall, mice fed with n‐3 PUFA supple-mentation displayed an emotional behavior profile and electrophysiological properties of medium spiny neurons which was distinct from the ones displayed by mice fed with the control diet, and this, independently of CSDS. Using the social interaction index to discriminate resilient and suscep-tible mice in the CSDS groups, n‐3 supplementation promoted resiliency. Altogether, our results pinpoint that exposure to a diet rich in LC n‐3 PUFA, as compared to a diet rich in SC n‐3 PUFA, influences the NAc fatty acid profile. In addition, electrophysiological properties and emotional behavior were altered in LC n‐3 PUFA mice, independently of CSDS. Our results bring new insights about the effect of LC n‐3 PUFA on emotional behavior and synaptic plasticity. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Dietary Long-Chain n-3 Polyunsaturated Fatty Acid Supplementation Alters Electrophysiological Properties in the Nucleus Accumbens and Emotional Behavior in Naïve and Chronically Stressed Mice

Long-chain (LC) n-3 polyunsaturated fatty acids (PUFAs) have drawn attention in the field of neuropsychiatric disorders, in particular depression. However, whether dietary supplementation with LC n-3 PUFA protects from the development of mood disorders is still a matter of debate. In the present study, we studied the effect of a two-month exposure to isocaloric diets containing n-3 PUFAs in the form of relatively short-chain (SC) (6% of rapeseed oil, enriched in α-linolenic acid (ALA)) or LC (6% of tuna oil, enriched in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) PUFAs on behavior and synaptic plasticity of mice submitted or not to a chronic social defeat stress (CSDS), previously reported to alter emotional and social behavior, as well as synaptic plasticity in the nucleus accumbens (NAc). First, fatty acid content and lipid metabolism gene expression were measured in the NAc of mice fed a SC (control) or LC n-3 (supplemented) PUFA diet. Our results indicate that LC n-3 supplementation significantly increased some n-3 PUFAs, while decreasing some n-6 PUFAs. Then, in another cohort, control and n-3 PUFA-supplemented mice were subjected to CSDS, and social and emotional behaviors were assessed, together with long-term depression plasticity in accumbal medium spiny neurons. Overall, mice fed with n-3 PUFA supplementation displayed an emotional behavior profile and electrophysiological properties of medium spiny neurons which was distinct from the ones displayed by mice fed with the control diet, and this, independently of CSDS. Using the social interaction index to discriminate resilient and susceptible mice in the CSDS groups, n-3 supplementation promoted resiliency. Altogether, our results pinpoint that exposure to a diet rich in LC n-3 PUFA, as compared to a diet rich in SC n-3 PUFA, influences the NAc fatty acid profile. In addition, electrophysiological properties and emotional behavior were altered in LC n-3 PUFA mice, independently of CSDS. Our results bring new insights about the effect of LC n-3 PUFA on emotional behavior and synaptic plasticity

N-3 Polyunsaturated Fatty Acids and the Resolution of Neuroinflammation

In the past few decades, as a result of their anti-inflammatory properties, n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFAs), have gained greater importance in the regulation of inflammation, especially in the central nervous system (in this case known as neuroinflammation). If sustained, neuroinflammation is a common denominator of neurological disorders, including Alzheimer's disease and major depression, and of aging. Hence, limiting neuroinflammation is a real strategy for neuroinflammatory disease therapy and treatment. Recent data show that n-3 LC-PUFAs exert anti-inflammatory properties in part through the synthesis of specialized pro-resolving mediators (SPMs) such as resolvins, maresins and protectins. These SPMs are crucially involved in the resolution of inflammation. They could be good candidates to resolve brain inflammation and to contribute to neuroprotective functions and could lead to novel therapeutics for brain inflammatory diseases. This review presents an overview 1) of brain n-3 LC-PUFAs as precursors of SPMs with an emphasis on the effect of n-3 PUFAs on neuroinflammation, 2) of the formation and action of SPMs in the brain and their biological roles, and the possible regulation of their synthesis by environmental factors such as inflammation and nutrition and, in particular, PUFA consumption

The effects of choline availability from gestation to early development on brain and retina function and phospholipid in a mice model

Choline is known to be essential for brain development and neural function, but its impact on the retina, as a type of neural tissue, is unknown. This study examined the effects of choline during fetal development on membrane phospholipid (PL) compositions and functions in neural tissues, brain and retina. Pregnant C57 BL/6 mice were fed one of the 4 choline modified diets from gestation to early development: i) deficient (Def, 0g/kg), ii) control (Cont, 2.5g/kg), iii) supplemented with choline chloride (Cho, 10g/kg), iv) supplemented with egg phosphatidylcholine (PC) (PC, 10g/kg). On postnatal day (PD) 7, pups were culled to 4 from each dam, and kept on the same respective diets until 45 PD. On PD 35, memory function was measured by Morris water maze and on PD 45, retina function by an electroretinogram. Brain and retina were obtained for PL analysis by 31P NMR. Animals on the Def and PC diets were lower in body weights on PD 7, in comparison to the other two groups. While the Def group caught up in weights to its Cont counterparts, the PC group’s weight stayed consistently low until PD 45 (P Def > PC > Cho, at all light intensities, without reaching statistical significances in cone-driven responses. There were no differences in major PL compositions in the brain and retina. PC enriched group had increased subclasses of ether PL, PEaa and PCaa in the brain. These results indicate that while the addition of choline supplementation is beneficial for fetal brain development and function during early developmental stages, its contributions in the retina were minor. The effect of choline to the membrane PL structure was negligible for the stage of development in the given experimental design.October 201

The Role of Dietary N-6 Polyunsaturated Fatty Acids on Lipid Mediators and Inflammation in the Mouse Brain

N-6 polyunsaturated fatty acids (PUFA) such as arachidonic acid (ARA, 20:4) and n-3 PUFA as docosahexaenoic acid (DHA, 22:6) are precursors to bioactive lipid mediators, which have important roles in many brain functions including inflammation. Previous studies have shown that dietary n-6 PUFA deprivation in pups can change brain ARA and DHA levels. However, the effects of n-6 PUFA deprivation on brain lipid metabolism during maternal stage has yet to be studied. Moreover, n-6 PUFA have been linked to the pathogenesis of many neurological disorders through many mechanisms, including conversion to ARA-derived lipid mediators (pro-inflammatory mediators) in the brain. Though diets low in n-6 PUFA are known to reduce levels of ARA and ARA-derived lipid mediators, no one has yet investigated the effects of lowering dietary n-6 PUFA on modulating brain inflammation and resolution in neuroinflammation. The first objective of this thesis was to examine how lowering dietary n-6 PUFA, from gestation, would change levels of hippocampal n-6 and n-3 PUFA and their lipid mediators in comparison to the offspring period. We found that maternal exposure to an n-6 PUFA deprived diet does not exacerbate the reduction in ARA and ARA-derived lipid mediators within hippocampal phospholipids (PL) relative to offspring exposure, which suggests that offspring exposure is a main regulating factor of these PUFA and their derivatives. Therefore, we used the offspring stage as the feeding period for the subsequent neuroinflammation study. Neuroinflammation was induced using intracerebroventricular injection of lipopolysaccharide (LPS) and the hippocampus was examined at several time points. Following LPS, different pro-inflammatory gene expression was associated with enrichment in gene expression categories associated with inflammation. However, these pro-inflammatory markers were not reduced by lowering dietary n-6 PUFA and importantly did not impair the resolution of neuroinflammation. In conclusion, we found that exposure of the offspring to an n-6 PUFA deprived diet was sufficient to lower the concentrations of ARA and other n-6 PUFA in hippocampal total PL. In a neuroinflammation model, the expression in gene ontology categories associated with inflammation was significantly increased and then resolved in response to LPS administration, however, irrespective of an n-6 PUFA diet.Ph.D

The Role of Dietary N-6 Polyunsaturated Fatty Acids on Lipid Mediators and Inflammation in the Mouse Brain

N-6 polyunsaturated fatty acids (PUFA) such as arachidonic acid (ARA, 20:4) and n-3 PUFA as docosahexaenoic acid (DHA, 22:6) are precursors to bioactive lipid mediators, which have important roles in many brain functions including inflammation. Previous studies have shown that dietary n-6 PUFA deprivation in pups can change brain ARA and DHA levels. However, the effects of n-6 PUFA deprivation on brain lipid metabolism during maternal stage has yet to be studied. Moreover, n-6 PUFA have been linked to the pathogenesis of many neurological disorders through many mechanisms, including conversion to ARA-derived lipid mediators (pro-inflammatory mediators) in the brain. Though diets low in n-6 PUFA are known to reduce levels of ARA and ARA-derived lipid mediators, no one has yet investigated the effects of lowering dietary n-6 PUFA on modulating brain inflammation and resolution in neuroinflammation. The first objective of this thesis was to examine how lowering dietary n-6 PUFA, from gestation, would change levels of hippocampal n-6 and n-3 PUFA and their lipid mediators in comparison to the offspring period. We found that maternal exposure to an n-6 PUFA deprived diet does not exacerbate the reduction in ARA and ARA-derived lipid mediators within hippocampal phospholipids (PL) relative to offspring exposure, which suggests that offspring exposure is a main regulating factor of these PUFA and their derivatives. Therefore, we used the offspring stage as the feeding period for the subsequent neuroinflammation study. Neuroinflammation was induced using intracerebroventricular injection of lipopolysaccharide (LPS) and the hippocampus was examined at several time points. Following LPS, different pro-inflammatory gene expression was associated with enrichment in gene expression categories associated with inflammation. However, these pro-inflammatory markers were not reduced by lowering dietary n-6 PUFA and importantly did not impair the resolution of neuroinflammation. In conclusion, we found that exposure of the offspring to an n-6 PUFA deprived diet was sufficient to lower the concentrations of ARA and other n-6 PUFA in hippocampal total PL. In a neuroinflammation model, the expression in gene ontology categories associated with inflammation was significantly increased and then resolved in response to LPS administration, however, irrespective of an n-6 PUFA diet.Ph.D

Chemical Approach to Separate Amino Alcohol Diastereomer Mixture

Identification of chiral compound has become the single most important research drug discovery since 1980. The advantage and disadvantage of having two isomers such as S or R rotation have been well documented in the literature. For example, Naproxen® commonly known as a nonsteroidal anti-inflammatory drug (NSAID). In its chemical structure, it has one chiral center which can provide a rotation of either R or S Naproxen®. The enantiomeric mixtures of Naproxen®, S-Naproxen® is one that used in pain relieve whereas the R- Naproxen® may give undesired side effect such as liver toxicity. Knowing how important separation of single isomer from the diastereomer mixture, my senior project is development of separating the diastereomer mixture using the chemical approach such as hydride mediated intramolecular cyclization. This project is a part of our on-going NP synthesis which has the significant relevant in anti-cancer research. In this poster, I am going to present three chemical steps leading into chemical separation of amino alcohol and provide with analytical data to confirm their chemical make-up.1st two chemical steps, CDI and NaBH4 reaction, are completed with their final yield calculation with the analytical data such as H1 NMR and C13 NMR are included in this poster. Addition to above two chemical steps, last stop of this project will be discussed and future direction of my research.   </jats:p

The Effect of Dairy Products and Nutrient Intake after Childbirth on the Risk of Postpartum Depression

Previous studies have shown an association between the intake of dairy products during pregnancy and reduced symptoms of postpartum depression (PPD). However, the effect of postpartum intake of dairy products on PPD is not fully understood. This study evaluates the effects of dairy products and nutrient intake after childbirth on the risk of PPD. A cross-sectional survey-based study was conducted asking participants to fill out a food frequency questionnaire (FFQ) to assess intake of dairy products and other nutrients. The Edinburgh Postnatal Depression Scale (EPDS) was used to screen for PPD symptoms. Out of 530 participants, almost three-quarters subjectively reported PPD (N = 395, 74.11%). The risk of PPD was relatively high for a Q1 level of consumption of all four dairy products and other nutrients, and from Q2 to Q4 there appeared to be an increase in the risk of PPD as consumption increased. However, after adjustment for confounding factors, there was no significant association between postpartum intake of dairy products and other nutrients and PPD. The results indicate that the potential of dairy products and nutrient intake to reduce PPD are minimal. Further longitudinal and intervention studies of dairy products and other (particularly anti-depressants) nutrients are required to draw firm conclusions about their associations with the risk of PPD

The impact of COVID-19 quarantine on dietary habits and physical activity in Saudi Arabia: a cross-sectional study

Abstract Background The COVID-19 pandemic has forced governments around the world to impose strict hygiene and national lockdown measures, which in turn has changed the dietary and lifestyle habits of the world’s population. Thus, the aim of this study is to evaluate whether dietary and physical activity behaviors of Saudi Arabia’s adult population changed during the COVID-19 quarantine. Methods An electronic questionnaire which assessed changes in body weight, dietary habits, and physical activity of Saudi Arabia’s adult population (n = 2255) during the COVID-19 quarantine was distributed on social media between June and July 2020. To test the differences between changes in dietary and physical activity behaviors in relation to changes in body weight a Chi-square test was used. Results Over 40 and 45% of participants reported eating and snacking more, respectively, which led to weight gain in around 28%. Most participants reported that they consumed home-cooked (73%) and healthy meals (47%), while only 7% reported that they consumed foods from restaurants. Feelings of boredom and emptiness (44%) and the availability of time for preparing meals (40%) were the main reasons for changing dietary habits. Honey (43%) and vitamin C (50%) were the most consumed immune-boosting food and dietary supplement, respectively. COVID-19 also had a negative impact on physical activity, lowering the practice in 52% subjects, which was associated with significant weight gain (p &lt; 0.001). Conclusion Assessing the changes to the population’s dietary habits and physical activity during the lockdown will help predict the outcome of the population’s future health and wellbeing after the pandemic. </jats:sec