Nutritional roles and therapeutic potentials of dietary sphingomyelin in brain diseases.

Sphingolipids have recently gained interest as potential players in variety of diseases due to their import roles in human body particularly, the brain. As sphingomyelin is the most common type of sphingolipids, deficits in its distribution to brain cells may contribute to neurological anomalies. However, data is limited regarding the impact of different levels of dietary sphingomyelin intake on neural function especially if this approach can boost cognition and prevent neurological disorders. This review evaluates the effect of dietary sphingomyelin and its metabolites (ceramide and sphingosine-1-phosphate) in animal models and in humans, with a primary focus on its impact on brain health. Additionally, it proposes multiple neuroenhancing effects of sphingomyelin-rich diet. This presents an opportunity to stimulate further research that aims to determine the therapeutic value of dietary sphingomyelin in preventing, improving or slowing the progression of central nervous system disorders.

Risk of Postpartum Depression: The Considerable Role of Maternal Health Status and Lifestyle.

Women's health issues are complex and require collaborative efforts to unravel some of these complexities. This study aims to identify the incidence risk of Postpartum Depression (PPD) in a national sample of women in Saudi Arabia and the relationship with several health status, lifestyle, and sociodemographic factors. A cross-sectional study with an online questionnaire format assessed the risk of postpartum depression using the Edinburgh Postnatal Depression Scale (EPDS) and included several questions on postpartum health status and lifestyle factors. Of the 550 women who responded to the survey 75% scored within range of risk for PPD (≥12). We found significant associations between family income, younger baby age, birth difficulty, having family support, level of physical activity, and the risk for PPD (p < 0.05). Urgent attention and resources should be directed towards screening and treatment for PPD in the healthcare system. The development of programs for awareness, education, and support of postpartum mothers in the Kingdom of Saudi Arabia is also required.

Dairy products intake and the risk of postpartum depression among mothers: A pilot study.

Introduction: Postpartum depression is a prevalent consequence of childbirth experienced by many women. There has been evidence linking dairy intake during pregnancy with a reduction in postpartum depression symptoms. However, there is still a lack of understanding regarding the effects of postpartum dairy consumption on postpartum depression. Objectives: To examine whether dairy products intake and calcium in dairy is associated with postpartum depression. Methods: A pilot study was conducted (n = 49 postpartum women). A food frequency questionnaire was used to evaluate the participants' consumption of calcium and dairy products during pregnancy, and the Edinburgh Postnatal Depression Scale was used to screen for postpartum depression symptoms. Results: Of 49 participants, 26 (53%) were at risk for postpartum depression (Edinburgh Postnatal Depression Scale ⩾ 12). Consuming >1 serving of Laban per day is significantly associated with reduced risk of postpartum depression (odds ratio = 0.01, 95% confidence interval [0, 0.3]). Total dairy intake >1 serving per day is significantly associated with reduced risk of postpartum depression (odds ratio = 0.17, 95% confidence interval [0.03, 0.83]). No significant association was found between the postpartum intake of milk, cheese, yogurt, or calcium and postpartum depression. Conclusion: Our findings indicate that higher total dairy intake was associated with a lower likelihood of postpartum depression. Further assessment with a larger sample size of participants could provide additional insight into the potential of dietary dairy to mitigate postpartum depression.

Investigating the quality of breakfast for female adolescents using a multi-method approach in Saudi Arabia: A cross-sectional study.

Breakfast has been shown to provide nutritional adequacy and improve the healthy lifestyle status of adolescents. However, limited information is available on the quality of breakfast among adolescents. Thus, this study aimed to evaluate the quality of breakfast among adolescents using a multiple-method approach in Saudi Arabia. This cross-sectional, school-based study was conducted in 3 public high schools in Al-Jumum, Saudi Arabia. High school females (n = 174) aged 15 to 18 years old were selected considering the regularity of consuming breakfast (≥ 4 d/wk and not after 10:00 a.m.). The quality of breakfast was assessed using 3 approaches: the modified Saudi food frequency questionnaire, the adapted method of breakfast quality, and the nutrient profile model. Sweet food items were consumed most frequently (64.9%, n = 113), followed by drinks (57.4%, n = 100), while the least frequently consumed items were sandwiches and burgers (43.52%, n = 76), snacks (41.9%, n = 72), and dairy and fats (41.8%, n = 71). The majority of breakfast eaters were classified as eating breakfasts of poor quality (50.6%), while the rest ate breakfasts of either good quality (38.1%) or very poor breakfast quality (10.8%). Based on the nutrient profile model of breakfast, high fat salt sugar (HFSS) food/drink items and non-HFSS items were consumed by 44.4% and 55.5% of the participants, respectively. This study showed that the majority of female adolescents consume poor-quality breakfast, mostly sweets and sweetened beverages. The nutrient content analysis emphasized these results by presenting a similar consumption of non-HFSS and HFSS breakfast foods. Future education programs on healthy breakfast options should be implemented among this population.

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.

Physical activity patterns among women during the postpartum period: an insight into the potential impact of perceived fatigue.

BACKGROUND: Regular participation in physical activity (PA) improves physical well-being and reduces the risk of contracting noncommunicable diseases. However, fatigue could negatively impact the PA participation of women in their postpartum period. This study delineated the levels of perceived fatigue and characterized the association between fatigue and the PA patterns of postpartum women. METHODS: A cross-sectional study was conducted using an online questionnaire distributed to postpartum women living in Saudi Arabia. Their perceived postpartum fatigue (PPF) was assessed using the fatigue severity scale; their PA, using the short form of the International Physical Activity Questionnaires; and their postpartum depression, using the Edinburgh Postnatal Depression Scale. Descriptive statistics were expressed as the mean ± standard deviation for normally distributed variables and as the median (interquartile range) for non-normally distributed variables. Between-group differences were tested using the Mann-Whitney U test for independent samples. To determine the relationship between the study variables, Spearman's rho correlation coefficient was calculated. Multiple linear regression analysis was performed to explain the role of fatigue severity as an independent predictor of the variance of the PA level. RESULTS: A total of 499 postpartum women were divided into the PPF group (43%), who self-reported fatigue, and the non-PPF group (57%), who self-reported no fatigue. There was a significant difference in the median of vigorous PA, and moderate PA which were significantly higher in the non-PPF group than in the PPF group. The women with PPF reported less engagement in walking and a longer sitting duration than the women without PPF. High fatigue severity was associated with lower moderate PA (ß = -10.90; p = .005; R2 = .21) and vigorous PA (ß = -04; p < .001; R2 = .13). These associations remained significant in the regression model after adjustment for the mother's depression score; age; number of children; body mass index (kg/m2); employment status; intake of vitamins B1 (thiamin), C, and D and of Omega-3; and walking metabolic equivalent. CONCLUSION: PPF may reduce the PA of postpartum women. Strategies targeting PPF may buffer its harmful impacts, and thus, improve postpartum women's health.

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.

The effect of choline availability from gestation to early development on brain and retina functions and phospholipid composition in a male mouse model.

OBJECTIVES: Although choline is essential for brain development and neural function, the effect of choline on retina function is not well understood. This study examined the effects of choline on neural tissues of brain and retina, and membrane phospholipid (PL) composition during fetal development. METHODS: Pregnant C57BL/6 mice were fed one of 4 choline modified diets: i) control (Cont, 2.5g/kg), ii) choline deficient (Def, 0g/kg), iii) supplemented with choline chloride (Cho, 10g/kg) and iv) supplemented with egg phosphatidylcholine (PC, 10g/kg). At postnatal day (PD) 21, pups were weaned onto their mothers' respective diets until PD 45. Spatial memory was measured using the Morris Water Maze; retina function by electroretinogram (ERG); and PL composition with nuclear magnetic resonance spectroscopy. RESULTS: Cho and PC supplementation enhanced cued learning and spatial memory abilities, respectively (p Def > PC > Cho, with no statistically significant alterations in cone-driven responses. There were no differences in the composition of major PLs in the brain and retina. In the brain, subclasses of ether PL, alkyl acyl- phosphatidylethanolamine (PEaa) and phosphatidylcholine (PCaa) were significantly greater among the PC supplemented group in comparison to the Def group. DISCUSSION: These results indicate that while choline supplementation during gestation to an early developmental period is beneficial for spatial memory, contributions to retina function are minor. Assessment with a larger sample size of retinas could warrant the essentiality of choline for retina development.

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

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 < 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.

The effects of n-6 polyunsaturated fatty acid deprivation on the inflammatory gene response to lipopolysaccharide in the mouse hippocampus.

BACKGROUND: Neuroinflammation is thought to contribute to psychiatric and neurological disorders such as major depression and Alzheimer's disease (AD). N-6 polyunsaturated fatty acids (PUFA) and molecules derived from them, including linoleic acid- and arachidonic acid-derived lipid mediators, are known to have pro-inflammatory properties in the periphery; however, this has yet to be tested in the brain. Lowering the consumption of n-6 PUFA is associated with a decreased risk of depression and AD in human observational studies. The purpose of this study was to investigate the inflammation-modulating effects of lowering dietary n-6 PUFA in the mouse hippocampus. METHODS: C57BL/6 male mice were fed either an n-6 PUFA deprived (2% of total fatty acids) or an n-6 PUFA adequate (23% of total fatty acids) diet from weaning to 12 weeks of age. Animals then underwent intracerebroventricular surgery, in which lipopolysaccharide (LPS) was injected into the left lateral ventricle of the brain. Hippocampi were collected at baseline and following LPS administration (1, 3, 7, and 14 days). A microarray (n = 3 per group) was used to identify candidate genes and results were validated by real-time PCR in a separate cohort of animals (n = 5-8 per group). RESULTS: Mice administered with LPS had significantly increased Gene Ontology categories associated with inflammation and immune responses. These effects were independent of changes in gene expression in any diet group. Results were validated for the effect of LPS treatment on astrocyte, cytokine, and chemokine markers, as well as some results of the diets on Ifrd2 and Mfsd2a expression. CONCLUSIONS: LPS administration increases pro-inflammatory and lipid-metabolizing gene expression in the mouse hippocampus. An n-6 PUFA deprived diet modulated inflammatory gene expression by both increasing and decreasing inflammatory gene expression, without impairing the resolution of neuroinflammation following LPS administration.

Oxylipin concentration, but not fatty acid composition, is altered in human donor milk pasteurised using both thermal and non-thermal techniques.

Human donor milk (DM) is Holder pasteurised (62·5°C, 30 min) to ensure its microbiological safety for infant consumption. In low-resource settings, flash heating is used to pasteurise milk. Although there is considerable interest in non-thermal alternatives (high hydrostatic pressure processing (HHP) and UVC irradiation) for pasteurisation, their effect on the fatty acid composition is not well understood. Of particular interest is the effect of pasteurisation on the generation of oxylipins. DM from eight mothers containing bacteria >5 × 107 colony-forming units/l was used. In a paired design, each pool of milk underwent four pasteurisation techniques: Holder; flash heating; UVC (250 nm, 25 min) and HHP (500 MPa, 8 min). Fatty acids were quantified by GC-flame ionisation detection and oxylipins derived from arachidonic acid; 18-carbon PUFA (α-linolenic acid, linoleic acid and γ-linolenic acid) and EPA/DHA were measured by liquid chromatography-tandem MS in aliquots of raw and processed milk. There were no significant changes to the composition of fatty acids following all pasteurisation techniques compared with raw milk. The n-6:n-3 ratio remained constant ranging from 6·4 to 6·6. Several arachidonic acid-derived oxylipins were highest post-UVC and elevated post-HHP compared with raw milk. Several oxylipins derived from 18-carbon PUFA (linoleic and α-linolenic acids) were elevated in UVC-treated milk. EPA/DHA-derived oxylipins were on average, unaffected by pasteurisation. Although some PUFA-derived oxylipins were increased following UVC and HHP, no method affected the fatty acid composition of human DM. Further research is needed to determine if varying levels of oxylipins in human DM as a result of processing can potentially mediate cellular signalling; proliferation and apoptosis, especially important for preterm infant development.

Maternal dietary n-6 polyunsaturated fatty acid deprivation does not exacerbate post-weaning reductions in arachidonic acid and its mediators in the mouse hippocampus.

OBJECTIVES: The present study examines how lowering maternal dietary n-6 polyunsaturated fatty acids (PUFA) (starting from pregnancy) compared to offspring (starting from post-weaning) affect the levels of n-6 and n-3 fatty acids in phospholipids (PL) and lipid mediators in the hippocampus of mice. METHODS: Pregnant mice were randomly assigned to consume either a deprived or an adequate n-6 PUFA diet during pregnancy and lactation (maternal exposure). On postnatal day (PND) 21, half of the male pups were weaned onto the same diet as their dams, and the other half were switched to the other diet for 9 weeks (offspring exposure). At PND 84, upon head-focused high-energy microwave irradiation, hippocampi were collected for PL fatty acid and lipid mediator analyses. RESULTS: Arachidonic acid (ARA) concentrations were significantly decreased in both total PL and PL fractions, while eicosapentaenoic acid (EPA) concentrations were increased only in PL fractions upon n-6 PUFA deprivation of offspring, regardless of maternal exposure. Several ARA-derived eicosanoids were reduced, while some of the EPA-derived eicosanoids were elevated by n-6 PUFA deprivation in offspring. There was no effect of diet on docosahexaenoic acid (DHA) or DHA-derived docosanoids concentrations under either maternal or offspring exposure. DISCUSSION: These results indicate that the maternal exposure to dietary n-6 PUFA may not be as important as the offspring exposure in regulating hippocampal ARA and some lipid mediators. Results from this study will be helpful in the design of experiments aimed at testing the significance of altering brain ARA levels over different stages of life.

Dietary fatty acids augment tissue levels of n-acylethanolamines in n-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) knockout mice.

N-acylethanolamines (NAEs) are lipid signaling mediators, which can be synthesized from dietary fatty acids via n-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD) and in turn influence physiological outcomes; however, the roles of NAPE-PLD upon dietary fatty acid modulation are not fully understood. Presently, we examine if NAPE-PLD is necessary to increase NAEs in response to dietary fatty acid manipulation. Post-weaning male wild-type (C57Bl/6), NAPE-PLD (-/+) and NAPE-PLD (-/-) mice received isocaloric fat diets containing either beef tallow, corn oil, canola oil or fish oil (10% wt/wt from fat) for 9 weeks. Brain docosahexaenoic acid (DHA) levels were higher (P<.01) in NAPE-PLD (-/+) (10.01±0.31 µmol/g) and NAPE-PLD (-/-) (10.89±0.61 µmol/g) than wild-type (7.72±0.61 µmol/g) consuming fish oil. In NAPE-PLD (-/-) mice, brain docosahexaenoylethanolamide (DHEA) levels were higher (P<.01) after fish oil feeding suggesting that NAPE-PLD was not necessary for DHEA synthesis. Liver and jejunum arachidonoylethanolamide, 1,2-arachidonoylglycerol and DHEA levels reflected their corresponding fatty acid precursors suggesting that alternate pathways are involved in NAE synthesis. NAPE-PLD (-/-) mice had lower oleoylethanolamide levels in the jejunum and a leaner phenotype compared to wild-type mice. Overall, these results demonstrate that dietary fatty acid can augment tissue NAEs in the absence of NAPE-PLD.

Docosahexaenoic acid (DHA) accretion in the placenta but not the fetus is matched by plasma unesterified DHA uptake rates in pregnant Long Evans rats.

Maternal delivery of docosahexaenoic acid (DHA, 22:6n-3) to the developing fetus via the placenta is required for fetal neurodevelopment, and is the only mechanism by which DHA can be accreted in the fetus. The aim of the current study was to utilize a balance model of DHA accretion combined with kinetic measures of serum unesterified DHA uptake to better understand the mechanism by which maternal DHA is delivered to the fetus via the placenta. Female rats maintained on a 2% α-linolenic acid diet free of DHA for 56 days were mated, and for balance analysis, sacrificed at 18 days of pregnancy, and fetus, placenta and maternal carcass fatty acid concentration were determined. For tissue DHA uptake, pregnant dams (14-18 days) were infused for 5 min with radiolabeled 14C-DHA and kinetic modeling was used to determine fetal and placental serum unesterified DHA uptake rates. DHA accretion rates in the fetus were determined to be 38 ± 2 nmol/d/g, 859 ± 100 nmol/d/litter and 74 ± 3 nmol/d/pup, which are all higher (P < 0.05) than the fetal serum unesterified DHA uptake rates of 16 ± 6 nmol/d/g, 239 ± 145 nmol/d/litter and 14 ± 8 nmol/d/pup. No differences (p > 0.05) in placental DHA accretion rates versus serum unesterified DHA uptake rates were observed as values varied only 6-35% between studies. No differences in placental accretion and uptake rates suggests that serum unesterified DHA is a significant pool for the maternal-placental transfer of DHA, and lower fetal DHA uptake compared to accretion supports remodeling of placental DHA for delivery to the fetus.

Maternal liver docosahexaenoic acid (DHA) stores are increased via higher serum unesterified DHA uptake in pregnant long Evans rats.

Maternal docosahexaenoic acid (DHA, 22:6n-3) supplies the developing fetus during pregnancy; however, the mechanisms are unclear. We utilized pregnant rats to determine rates of DHA accretion, tissue unesterified DHA uptake and whole-body DHA synthesis-secretion. Female rats maintained on a DHA-free, 2% α-linolenic acid diet were either:1) sacrificed at 56 days for baseline measures, 2) mated and sacrificed at 14-18 days of pregnancy or 3) or sacrificed at 14-18 days as age-matched virgin controls. Maternal brain, adipose, liver and whole body fatty acid concentrations was determined for balance analysis, and kinetic modeling was used to determine brain and liver plasma unesterified DHA uptake and whole-body DHA synthesis-secretion rates. Total liver DHA was significantly higher in pregnant (95±5 µmol) versus non-pregnant (49±5) rats with no differences in whole-body DHA synthesis-secretion rates. However, liver uptake of plasma unesterified DHA was 3.8-fold higher in pregnant animals compared to non-pregnant controls, and periuterine adipose DHA was lower in pregnant (0.89±0.09 µmol/g) versus non-pregnant (1.26±0.06) rats. In conclusion, higher liver DHA accretion during pregnancy appears to be driven by higher unesterified DHA uptake, potentially via DHA mobilization from periuterine adipose for delivery to the fetus during the brain growth spurt.

Lowering dietary n-6 polyunsaturated fatty acids: interaction with brain arachidonic and docosahexaenoic acids.

PURPOSE OF REVIEW: Arachidonic (ARA) and docosahexaenoic (DHA) acids are the most abundant polyunsaturated fatty acids (PUFA) in the brain, where they have many biological effects, including on inflammation, cell-signaling, appetite regulation, and blood flow. The Western diet contains a high ratio of n-6: n-3 PUFA. Although interest in lowering this ratio has largely focused on increasing intake of n-3 PUFA, few studies have examined lowering dietary n-6 PUFA. This review will evaluate the effect of lowering dietary n-6 PUFA on levels and metabolism of ARA and DHA in animal models and in humans, with a primary focus on the brain. RECENT FINDINGS: In animal models, lowering dietary ARA or linoleic acid generally lowers levels of brain ARA and raises DHA. Lowering dietary n-6 PUFA can also modulate the levels of ARA and DHA metabolizing enzymes, as well as their associated bioactive mediators. Human studies examining changes in plasma fatty acid composition following n-6 PUFA lowering demonstrate no changes in levels of ARA and DHA, though there is evidence of alterations in their respective bioactive mediators. SUMMARY: Lowering dietary n-6 PUFA, in animal models, can alter the levels and metabolism of ARA and DHA in the brain, but it remains to be determined whether these changes are clinically meaningful.

Morris Water Maze Training in Mice Elevates Hippocampal Levels of Transcription Factors Nuclear Factor (Erythroid-derived 2)-like 2 and Nuclear Factor Kappa B p65.

Research has identified several transcription factors that regulate activity-dependent plasticity and memory, with cAMP-response element binding protein (CREB) being the most well-studied. In neurons, CREB activation is influenced by the transcription factor nuclear factor kappa B (NF-κB), considered central to immunity but more recently implicated in memory. The transcription factor early growth response-2 (Egr-2), an NF-κB gene target, is also associated with learning and memory. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an antioxidant transcription factor linked to NF-κB in pathological conditions, has not been studied in normal memory. Given that numerous transcription factors implicated in activity-dependent plasticity demonstrate connections to NF-κB, this study simultaneously evaluated protein levels of NF-κB, CREB, Egr-2, Nrf2, and actin in hippocampi from young (1 month-old) weanling CD1 mice after training in the Morris water maze, a hippocampal-dependent spatial memory task. After a 6-day acquisition period, time to locate the hidden platform decreased in the Morris water maze. Mice spent more time in the target vs. non-target quadrants of the maze, suggestive of recall of the platform location. Western blot data revealed a decrease in NF-κB p50 protein after training relative to controls, whereas NF-κB p65, Nrf2 and actin increased. Nrf2 levels were correlated with platform crosses in nearly all tested animals. These data demonstrate that training in a spatial memory task results in alterations in and associations with particular transcription factors in the hippocampus, including upregulation of NF-κB p65 and Nrf2. Training-induced increases in actin protein levels caution against its use as a loading control in immunoblot studies examining activity-dependent plasticity, learning, and memory.