Brain α-Tocopherol Concentration and Stereoisomer Profile Alter Hippocampal Gene Expression in Weanling Mice

ABSTRACT Background Alpha-tocopherol (αT), the bioactive constituent of vitamin E, is essential for fertility and neurological development. Synthetic αT (8 stereoisomers; all rac-αT) is added to infant formula at higher concentrations than natural αT (RRR-αT only) to adjust for bio-potency differences, but its effects on brain development are poorly understood. Objectives The objective was to determine the impact of bio-potency–adjusted dietary all rac-αT versus RRR-αT, fed to dams, on the hippocampal gene expression in weanling mice. Methods Male/female pairs of C57BL/6J mice were fed AIN 93-G containing RRR-αT (NAT) or all rac-αT (SYN) at 37.5 or 75 IU/kg (n = 10/group) throughout gestation and lactation. Male pups were euthanized at 21 days. Half the brain was evaluated for the αT concentration and stereoisomer distribution. The hippocampus was dissected from the other half, and RNA was extracted and sequenced. Milk αT was analyzed in separate dams. Results A total of 797 differentially expressed genes (DEGs) were identified in the hippocampi across the 4 dietary groups, at a false discovery rate of 10%. Comparing the NAT-37.5 group to the NAT-75 group or the SYN-37.5 group to the SYN-75 group, small differences in brain αT concentrations (10%; P < 0.05) led to subtle changes (<10%) in gene expression of 600 (NAT) or 487 genes (SYN), which were statistically significant. Marked differences in brain αT stereoisomer profiles (P < 0.0001) had a small effect on fewer genes (NAT-37.5 vs. SYN-37.5, 179; NAT-75 vs. SYN-75, 182). Most of the DEGs were involved in transcription regulation and synapse formation. A network analysis constructed around known vitamin E interacting proteins (VIPs) revealed a group of 32 DEGs between NAT-37.5 vs. SYN-37.5, explained by expression of the gene for the VIP, protein kinase C zeta (Pkcz). Conclusions In weanling mouse hippocampi, a network of genes involved in transcription regulation and synapse formation was differentially affected by dam diet αT concentration and source: all rac-αT or RRR-αT.

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The Oral Intake of Organic Germanium, Ge-132, Elevates α-Tocopherol Levels in the Plas-ma and Modulates Hepatic Gene Expression Profiles to Promote Immune Activation in Mice

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000205 ◽

2014 ◽

Vol 84 (3-4) ◽

pp. 0183-0195 ◽

Cited By ~ 12

Author(s):

Takashi Nakamura ◽

Tomoya Takeda ◽

Yoshihiko Tokuji

Keyword(s):

Gene Expression ◽

Immune Activation ◽

Expression Profiles ◽

Water Soluble ◽

Alpha Tocopherol ◽

Hepatic Gene Expression ◽

Tocopherol Concentration ◽

Altered Expression ◽

Atp Production ◽

Transfer Protein

The common water-soluble organic germanium compound poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) exhibits activities related to immune responses and antioxidant induction. In this study, we evaluated the antioxidative effect of dietary Ge-132 in the plasma of mice. Male ICR mice (seven mice per group) received an AIN-76 diet with 0.05 % Ge-132; three groups received the Ge-132-containing diet for 0, 1 or 4 days. The plasma alpha-tocopherol (α-tocopherol) concentration increased from 6.85 to 9.60 μg/ml after 4 days of Ge-132 intake (p < 0.05). We evaluated the changes in hepatic gene expression related to antioxidative activity as well as in the entire expression profile after one day of Ge-132 intake, using DNA microarray technology. We identified 1,220 genes with altered expression levels greater than 1.5-fold (increased or decreased) as a result of Ge-132 intake, and α-tocopherol transfer protein (Ttpa) gene expression was increased 1.62-fold. Immune activation was identified as the category with the most changes (containing 60 Gene Ontology (GO) term biological processes (BPs), 41 genes) via functional clustering analysis of altered gene expression. Ge-132 affected genes in clusters related to ATP production (22 GO term BPs, 21 genes), lipid metabolism (4 GO term BPs, 38 genes) and apoptosis (5 GO term BPs). Many GO term BPs containing these categories were significantly affected by the Ge-132 intake. Oral Ge-132 intake may therefore have increased plasma α-tocopherol levels by up-regulating α-tocopherol transfer protein (Ttpa) gene expression.

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Alpha Tocopherol Loaded in Liposome: Preparation, Optimization, Characterization and Sperm Motility Protection

Drug Delivery Letters ◽

10.2174/2210303110666200302113209 ◽

2020 ◽

Vol 10 (3) ◽

pp. 228-236 ◽

Cited By ~ 1

Author(s):

Lamia Taouzinet ◽

Sofiane Fatmi ◽

Allaeddine Khellouf ◽

Mohamed Skiba ◽

Mokrane Iguer-ouada

Keyword(s):

Vitamin E ◽

Sperm Motility ◽

High Performance ◽

Positive Impact ◽

Alpha Tocopherol ◽

Ethanol Injection ◽

Liposome Preparation ◽

Liposome Size ◽

Optimum Solution ◽

The Impact

Background: Alpha-tocopherol is a potent antioxidant involved in sperm protection particularly during cryopreservation. However, its poor solubility limits the optimal protection in aqueous solutions. Objective: The aim of this study was to enhance the solubility of α-tocopherol by the use of liposomes. Methods: The experimental approach consisted to load vitamin E in liposomes prepared by ethanol injection method and the optimization carried out by an experimental design. The optimum solution was characterized by high performance liquid chromatography and scanning electron microscope. Finely, the impact on sperm motility protection was studied by the freezing technic of bovine sperm. Results: The optimum solution was obtained when using 10.9 mg/ml of phospholipids, 1.7 mg/ml of cholesterol and 2 mg/ml of vitamin E. The liposome size was 99.86 nm, providing 78.47% of loaded efficiency. The results showed also a significant positive impact on sperm motility after hours of preservation. Conclusion: In conclusion, the current results showed the interest of liposome preparation as an alternative to enhance vitamin E solubility and to protect spermatozoa during cryopreservation.

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Microglia motility depends on neuronal activity and promotes structural plasticity in the hippocampus

10.1101/515759 ◽

2019 ◽

Cited By ~ 1

Author(s):

Felix C. Nebeling ◽

Stefanie Poll ◽

Lena C. Schmid ◽

Manuel Mittag ◽

Julia Steffen ◽

...

Keyword(s):

Neuronal Activity ◽

Dendritic Spines ◽

Synapse Formation ◽

Brain Parenchyma ◽

Two Photon ◽

Contact Rates ◽

Health And Disease ◽

The Impact ◽

The Brain

AbstractMicroglia, the resident immune cells of the brain, play a complex role in health and disease. They actively survey the brain parenchyma by physically interacting with other cells and structurally shaping the brain. Yet, the mechanisms underlying microglia motility and their significance for synapse stability, especially during adulthood, remain widely unresolved. Here we investigated the impact of neuronal activity on microglia motility and its implication for synapse formation and survival. We used repetitive two-photon in vivo imaging in the hippocampus of awake mice to simultaneously study microglia motility and their interaction with synapses. We found that microglia process motility depended on neuronal activity. Simultaneously, more dendritic spines emerged in awake compared to anesthetized mice. Interestingly, microglia contact rates with individual dendritic spines were associated with their stability. These results suggest that microglia are not only sensing neuronal activity, but participate in synaptic rewiring of the hippocampus during adulthood, which has profound relevance for learning and memory processes.

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The Role of Vitamin E in the Treatment of NAFLD

Diseases ◽

10.3390/diseases6040086 ◽

2018 ◽

Vol 6 (4) ◽

pp. 86 ◽

Cited By ~ 21

Author(s):

Brandon Perumpail ◽

Andrew Li ◽

Nimy John ◽

Sandy Sallam ◽

Neha Shah ◽

...

Keyword(s):

Vitamin E ◽

Nonalcoholic Steatohepatitis ◽

Medical Literature ◽

Ease Of Use ◽

Alpha Tocopherol ◽

Diabetic Patients ◽

Nonalcoholic Fatty Liver ◽

Therapeutic Choice ◽

The Impact

There has been a growing interest in the role of vitamin E supplementation in the treatment and/or prevention of nonalcoholic fatty liver (NAFLD). We performed a systematic review of the medical literature from inception through 15 June 2018 by utilizing PubMed and searching for key terms such as NAFLD, vitamin E, alpha-tocopherol, and nonalcoholic steatohepatitis (NASH). Data from studies and medical literature focusing on the role of vitamin E therapy in patients with NAFLD and nonalcoholic steatohepatitis (NASH) were reviewed. Most studies assessing the impact of vitamin E in NAFLD were designed to evaluate patients with NASH with documented biochemical and histological abnormalities. These studies demonstrated improvement in biochemical profiles, with a decline in or normalization of liver enzymes. Furthermore, histological assessment showed favorable outcomes in lobular inflammation and hepatic steatosis following treatment with vitamin E. Current guidelines regarding the use of vitamin E in the setting of NAFLD recommend that vitamin E-based treatment be restricted to biopsy-proven nondiabetic patients with NASH only. However, some concerns have been raised regarding the use of vitamin E in patients with NASH due to its adverse effects profile and lack of significant improvement in hepatic fibrosis. In conclusion, the antioxidant, anti-inflammatory, and anti-apoptotic properties of vitamin E accompanied by ease-of-use and exceptional tolerability have made vitamin E a pragmatic therapeutic choice in non-diabetic patients with histologic evidence of NASH. Future clinical trials with study design to assess vitamin E in combination with other anti-fibrotic agents may yield an additive or synergistic therapeutic effect.

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Selenium and α-tocopherol content in eggs produced by hens that were fed diets supplemented with selenomethionine, sodium selenite and vitamin E

Czech Journal of Animal Science ◽

10.17221/92/2010-cjas ◽

2010 ◽

Vol 55 (No. 9) ◽

pp. 388-397 ◽

Cited By ~ 9

Author(s):

M. Skřivan ◽

I. Bubancová ◽

M. Marounek ◽

G. Dlouhá

Keyword(s):

Vitamin E ◽

Sodium Selenite ◽

Thiobarbituric Acid ◽

Basal Diet ◽

Tocopherol Content ◽

Alpha Tocopherol ◽

Dietary Vitamin ◽

Tocopherol Concentration ◽

The Third ◽

Egg Yolks

The effect of supplementing dietary selenium (Se) and vitamin E was investigated in 330 24-week-old laying hens. The hens were fed a basal diet containing Se and α-tocopherol at 0.11 and 26 mg/kg, respectively, or a diet supplemented with Se at 0.3 mg/kg and vitamin E between 0 and 625 mg/kg. Se was supplied as Se-methionine or sodium selenite. The eggs were collected for analysis during the third, seventh and eleventh weeks of the experiment. Supplementation of either form of Se significantly increased the Se concentration in egg yolks and whites, with a more pronounced effect caused by Se-methionine. The egg yolk α-tocopherol concentration paralleled the dietary α-tocopherol concentration. At a high dietary α-tocopherol concentration (632 mg/kg), the retinol content in egg yolks from hens fed Se-methionine increased significantly. Supplementation of Se-methionine significantly increased the α-tocopherol content in the eggs in the third and seventh weeks of the experiment. A moderate decrease in yolk cholesterol was observed in hens fed Se-methionine and α-tocopherol at 119 mg/kg. The concentration of products from lipid peroxidation (thiobarbituric acid-reactive substances, TBARS) in egg yolks increased marginally during the refrigerated storage of the eggs for 2 weeks. The effect of dietary vitamin E on TBARS formation was generally small, although a more significant effect was observed at the highest dose tested.

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Region-specific Foxp2 deletions in cortex, striatum or cerebellum cannot explain vocalization deficits observed in spontaneous global knockouts

Scientific Reports ◽

10.1038/s41598-020-78531-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Bastiaan H. A. Urbanus ◽

Saša Peter ◽

Simon E. Fisher ◽

Chris I. De Zeeuw

Keyword(s):

Gene Expression ◽

Language Comprehension ◽

Motor Performance ◽

Broadband Noise ◽

Conditional Knockout ◽

Ultrasonic Vocalizations ◽

Rare Mutations ◽

Key Sites ◽

The Impact ◽

The Brain

AbstractFOXP2 has been identified as a gene related to speech in humans, based on rare mutations that yield significant impairments in speech at the level of both motor performance and language comprehension. Disruptions of the murine orthologue Foxp2 in mouse pups have been shown to interfere with production of ultrasonic vocalizations (USVs). However, it remains unclear which structures are responsible for these deficits. Here, we show that conditional knockout mice with selective Foxp2 deletions targeting the cerebral cortex, striatum or cerebellum, three key sites of motor control with robust neural gene expression, do not recapture the profile of pup USV deficits observed in mice with global disruptions of this gene. Moreover, we observed that global Foxp2 knockout pups show substantive reductions in USV production as well as an overproduction of short broadband noise “clicks”, which was not present in the brain region-specific knockouts. These data indicate that deficits of Foxp2 expression in the cortex, striatum or cerebellum cannot solely explain the disrupted vocalization behaviours in global Foxp2 knockouts. Our findings raise the possibility that the impact of Foxp2 disruption on USV is mediated at least in part by effects of this gene on the anatomical prerequisites for vocalizing.

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Alpha-tocopherol, an effective inhibitor of platelet adhesion

Blood ◽

10.1182/blood.v73.1.141.141 ◽

1989 ◽

Vol 73 (1) ◽

pp. 141-149 ◽

Cited By ~ 65

Author(s):

J Jandak ◽

M Steiner ◽

PD Richardson

Keyword(s):

Vitamin E ◽

Platelet Adhesion ◽

Ex Vivo ◽

Platelet Rich Plasma ◽

Flow Chamber ◽

Alpha Tocopherol ◽

Tocopherol Concentration ◽

Average Decrease ◽

Platelet Adherence

Abstract Platelet adhesiveness was tested ex vivo in a group of six normal individuals receiving varying doses of alpha-tocopherol. Adhesion to glass slides coated with fibronectin, collagen, fibrinogen, or plasma proteins was studied by perfusing platelet-rich plasma through a flow chamber that allowed time- and space-resolved observations of platelet adhesion. Platelet adherence was measured in an area of parallel flow lines and low shear rate under standardized conditions before and after dietary supplementation with vitamin E at doses of 200 and 400 IU/d. Platelet adherence differed in magnitude depending on the adhesive surface. There was a distinct preference of platelets to adhere to sites that had been previously occupied. A remarkable decrease in platelet adherence was observed after vitamin E supplementation. The average decrease in adhesion after 2 weeks of 200 IU vitamin E was 75%. After 2 weeks of 400 IU vitamin E, platelet adhesion was reduced by 82%. The inhibitory activity of alpha-tocopherol was dose dependent and correlated well with the increase in alpha-tocopherol concentration in platelets after supplementation. Scanning electron microscopy revealed a striking decrease of pseudopodium formation in alpha-tocopherol- enriched platelets. Our results suggest that vitamin E may also be an effective antiadhesive agent in vivo.

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Alpha-tocopherol, an effective inhibitor of platelet adhesion

Blood ◽

10.1182/blood.v73.1.141.bloodjournal731141 ◽

1989 ◽

Vol 73 (1) ◽

pp. 141-149

Author(s):

J Jandak ◽

M Steiner ◽

PD Richardson

Keyword(s):

Vitamin E ◽

Platelet Adhesion ◽

Ex Vivo ◽

Platelet Rich Plasma ◽

Flow Chamber ◽

Alpha Tocopherol ◽

Tocopherol Concentration ◽

Average Decrease ◽

Platelet Adherence

Platelet adhesiveness was tested ex vivo in a group of six normal individuals receiving varying doses of alpha-tocopherol. Adhesion to glass slides coated with fibronectin, collagen, fibrinogen, or plasma proteins was studied by perfusing platelet-rich plasma through a flow chamber that allowed time- and space-resolved observations of platelet adhesion. Platelet adherence was measured in an area of parallel flow lines and low shear rate under standardized conditions before and after dietary supplementation with vitamin E at doses of 200 and 400 IU/d. Platelet adherence differed in magnitude depending on the adhesive surface. There was a distinct preference of platelets to adhere to sites that had been previously occupied. A remarkable decrease in platelet adherence was observed after vitamin E supplementation. The average decrease in adhesion after 2 weeks of 200 IU vitamin E was 75%. After 2 weeks of 400 IU vitamin E, platelet adhesion was reduced by 82%. The inhibitory activity of alpha-tocopherol was dose dependent and correlated well with the increase in alpha-tocopherol concentration in platelets after supplementation. Scanning electron microscopy revealed a striking decrease of pseudopodium formation in alpha-tocopherol- enriched platelets. Our results suggest that vitamin E may also be an effective antiadhesive agent in vivo.

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Vitamin E activates CRABP-II gene expression in cultured human fibroblasts, role of protein kinase C

FEBS Letters ◽

10.1016/j.febslet.2004.05.073 ◽

2004 ◽

Vol 569 (1-3) ◽

pp. 240-244 ◽

Cited By ~ 12

Author(s):

Amparo Gimeno ◽

Rosa Zaragozá ◽

Juan R Viña ◽

Vicente J Miralles

Keyword(s):

Gene Expression ◽

Protein Kinase C ◽

Vitamin E ◽

Protein Kinase ◽

Human Fibroblasts ◽

Kinase C ◽

Cultured Human Fibroblasts ◽

Crabp Ii

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Determination of vitamin E in microsamples of serum by liquid chromatography with electrochemical detection.

Clinical Chemistry ◽

10.1093/clinchem/31.6.880 ◽

1985 ◽

Vol 31 (6) ◽

pp. 880-882 ◽

Cited By ~ 17

Author(s):

P P Chou ◽

P K Jaynes ◽

J L Bailey

Keyword(s):

Liquid Chromatography ◽

Vitamin E ◽

Electrochemical Detection ◽

High Performance ◽

Internal Standard ◽

Small Sample ◽

Alpha Tocopherol ◽

Tocopherol Concentration ◽

Minimum Concentration

Abstract In this procedure for determination of vitamin E by "high-performance" liquid chromatography with electrochemical detection, 25-microL serum specimens are deproteinized with ethanol. Vitamin E (alpha-tocopherol), its derivatives (beta- and gamma-tocopherols), and the internal standard (delta-tocopherol) are extracted into heptane and the extract is evaporated and the residue reconstituted with methanol before injection into the chromatograph. Within- and between-run CVs for an alpha-tocopherol concentration of 13.6 mg/L were 5.1% (n = 28) and 6.0% (n = 5), respectively. The standard curve is linear to 100 mg/L; the minimum concentration detectable is 0.1 mg/L. Analytical recovery ranged from 99.8% to 104.8%. In 36 specimens collected from apparently healthy subjects who were not taking vitamin supplements, alpha-tocopherol as determined by this method ranged from 4.3 to 9.7 mg/L, from 1.8 to 3.9 mg/L for beta- and gamma-tocopherols. Results by this method (y) and an HPLC-ultraviolet method (x) correlate reasonably (r = 0.81): y = 0.88x - 0.55 mg/L (n = 45). This procedure is adaptable to automated analysis, and the small sample requirement facilitates its applicability to neonates.

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