The effects of prenatal and early postnatal tocotrienol-rich fraction supplementation on cognitive function development in male offspring rats

Abstract

Background: Recent findings suggest that the intake of specific nutrients during the critical period in early life influence cognitive and behavioural development profoundly. Antioxidants such as vitamin E have been postulated to be pivotal in this process, as vitamin E is able to protect the growing brain from oxidative stress. Currently tocotrienols are gaining much attention due to their potent antioxidant and neuroprotective properties. It is thus compelling to look at the effects of prenatal and early postnatal tocotrienols supplementation, on cognition and behavioural development among offsprings of individual supplemented with tocotrienols. Therefore, this study is aimed to investigate potential prenatal and early postnatal influence of Tocotrienol-Rich Fraction (TRF) supplementation on cognitive function development in male offspring rats. Eight-week-old adult female Sprague Dawley (SD) rats were randomly assigned into five groups of two animals each. The animals were fed either with the base diet as control (CTRL), base diet plus vehicle (VHCL), base diet plus docosahexanoic acid (DHA), base diet plus Tocotrienol-Rich fraction (TRF), and base diet plus both docosahexaenoic acid, and tocotrienol rich fraction (DTRF) diets for 2 weeks prior to mating. The females (F0 generation) were maintained on their respective treatment diets throughout the gestation and lactation periods. Pups (F1 generation) derived from these dams were raised with their dams from birth till four weeks post natal. The male pups were weaned at 8 weeks postnatal, after which they were grouped into five groups of 10 animals each, and fed with the same diets as their dams for another eight weeks. Learning and behavioural experiments were conducted only in male off-spring rats using the Morris water maze. Eight-week-old adult female Sprague Dawley (SD) rats were randomly assigned into five groups of two animals each. The animals were fed either with the base diet as control (CTRL), base diet plus vehicle (VHCL), base diet plus docosahexanoic acid (DHA), base diet plus Tocotrienol-Rich fraction (TRF), and base diet plus both docosahexaenoic acid, and tocotrienol rich fraction (DTRF) diets for 2 weeks prior to mating. The females (F0 generation) were maintained on their respective treatment diets throughout the gestation and lactation periods. Pups (F1 generation) derived from these dams were raised with their dams from birth till four weeks post natal. The male pups were weaned at 8 weeks postnatal, after which they were grouped into five groups of 10 animals each, and fed with the same diets as their dams for another eight weeks. Learning and behavioural experiments were conducted only in male off-spring rats using the Morris water maze.

Results: Results showed that prenatal and postnatal TRF supplementation increased the brain (4-6 fold increase) and plasma α-tocotrienol (0.8 fold increase) levels in male off-springs. There is also notably better cognitive performance based on the Morris water maze test among these male off-springs.

Conclusion: Based on these results, it is concluded that prenatal and postnatal TRF supplementation improved cognitive function development in male progeny rats.

Figure 1

Vitamin E levels in the plasman of male offspring rats accross treatment groups. A) Tocotrienol B) α-tocopherol. Values are means ± SD, n = 10. Significantly different from the control group, *P ≤ 0.001 and **P ≤ 0.05.

Figure 2

Brain α- tocotrienol and α-tocopherols contents across treatment groups. Values are means ± SD (n = 10). Significantly different from the control group, *P < 0.001, **P < 0.01 and ***P < 0.05.

Figure 3

Effects of Tocotrienol-Rich Fraction (TRF) supplementation on escape latencies across treatment groups throughout the 5 day acquisition phase. Data expressed as mean ± SD (n = 10). **P < 0.01 and ***P < 0.05 denotes significant difference from the control group.

Figure 4

Effects of Tocotrienol-Rich Fraction (TRF) supplementation on the average swimming speed across treatment groups throughout the 5 day acquisition phase. Data expressed as mean ± SD (n = 10). No significant difference (P > 0.05) between treatment groups and the control group.

Figure 5

Effects of Tocotrienol-Rich Fraction (TRF) supplementation on distance travelled across treatment groups throughout the 5 day acquisition phase. Data expressed as mean ± SD (n = 10).* P < 0.001 **P < 0.01 and ***P < 0.05 denotes significant difference from the control group.

Figure 6

Acquisition probe trial results across treatment groups. Data are shown as means ± SD (n = 10). Time spent (sec), time spent in the SW quadrant, where the platform was positioned during acquisition trial; # entries, number of entries into the SW quadrant; # line crossing, number of crossing of the platform position; Average duration SW quadrant (sec), average duration spent in the SW quadrant. Significantly different from the control group, **P < 0.05.

Figure 7

Effects of Tocotrienol-Rich Fraction (TRF) supplementation on escape latencies across treatment groups throughout the 5 day reversal phase. Data expressed as mean ± SD (n = 10). *P < 0.001, **P < 0.01 and ***P < 0.05 denotes significant difference from the control group.

Figure 8

Effects of Tocotrienol-Rich Fraction (TRF) supplementation on distance travelled across treatment groups throughout the 5 day reversal phase. Data expressed as mean ± SD (n = 10). **P < 0.01 and ***P < 0.05 denotes significant difference from the control group.

Figure 9

Reverse probe trial results across treatment groups. Data are shown as means ± SD (n = 10). Time spent (sec), time spent in the SW quadrant, where the platform was positioned during acquisition trial; # entries, number of entries into the SW quadrant; # line crossing, number of crossing of the platform position; Average duration SW quadrant (sec), average duration spent in the SW quadrant. Significantly different from the control group, *P < 0.001 and **P < 0.01.

Figure 10

Flow diagram illustrating experimental events.