Tocotrienol Rich Fraction Reverses Age‐Related Deficits in Spatial Learning and Memory in Aged Rats

Abstract

Little is known about the effect of vitamin E on brain function. Therefore, in this study we evaluated the effect of tocotrienol rich fraction (TRF) on behavioral impairment and oxidative stress in aged rats. Thirty-six male Wistar rats (young: 3-months-old; aged: 21-months-old) were treated with either the control (olive oil) or TRF (200 mg/kg) for 3 months. Behavioral studies were performed using the open field test and Morris water maze (MWM) task. Blood was taken for assessment of DNA damage, plasma malondialdehyde (MDA) and vitamin E, and erythrocyte antioxidant enzyme activity. Brains were also collected to measure vitamin E levels. Results showed that aged rats exhibited reduced exploratory activity, enhanced anxiety and decreased spatial learning and memory compared with young rats. DNA damage and plasma MDA were increased, and vitamin E levels in plasma and brain were reduced in aged rats. Aged rats supplemented with TRF showed a markedly reduced level of anxiety, improved spatial learning and memory, reduced amount and severity of DNA damage, a reduced level of MDA, and increased levels of antioxidant enzyme activity and plasma/brain vitamin E compared with age-matched controls. In conclusion, TRF supplementation reverses spatial learning and memory decline and decreases oxidative stress in aged rats.

α-Tocopherol and Hippocampal Neural Plasticity in Physiological and Pathological Conditions

“…Besides α-T, other members of the vitamin E family, i.e., tocotrienols (natural compounds present in select vegetable oils, as palm oil), have also been reported to rescue age-related deficits in neuroplasticity and cognition. Adult and old rats supplemented for 8 and 3 months, respectively, with a tocotrienol-rich fraction (200 mg/kg/day) displayed higher spatial learning and memory performance, reduced amount and severity of DNA damage, decreased level of oxidative markers such as malondialdehyde, as well as increased levels of antioxidant enzyme activity and brain vitamin E compared with age-matched, non-supplemented controls [133,134]. …”

Alpha-Tocotrienol Prevents Oxidative Stress-Mediated Post-Translational Cleavage of Bcl-xL in Primary Hippocampal Neurons

“…Long-term supplementation with a tocotrienol-rich fraction (TRF) to AβPP/PS1 transgenic mice expressing amyloid protein precursor attenuated amyloid beta deposition in the brain and improved cognition [43][44][45]. Aged rats supplemented with TRF also showed improved spatial learning and memory and reduced anxiety levels [46].…”

Modulation of Proteome Profile in AβPP/PS1 Mice Hippocampus, Medial Prefrontal Cortex, and Striatum by Palm Oil Derived Tocotrienol-Rich Fraction

“…Vitamin E plays a central role in scavenging peroxyl radical, preventing lipid peroxidation, and protecting polyunsaturated fatty acids (PUFAs) and other cell membranes components and lipoproteins from oxidation by free radicals [68]. Tocotrienols in particular have been shown previously to exert antioxidative effect in in vitro and in vivo studies [69][70][71]. For instance, up to 100 mol/L of ␥tocotrienol concentration protected against hydrogen peroxide (H 2 O 2 )-induced cell death and apoptosis in primary astrocyte cultures [69].…”

“…In addition, ␣-tocotrienol has been shown to protect neuronal cell from glutamate-induced toxicity primarily by a direct antioxidant action [70]. In an in vivo study, three months supplementation of TRF (200 mg/kg) has been reported to markedly reduce lipid peroxidation, modulate antioxidant enzymes activity and brain arginine metabolism, and also improve memory in aged rats [19,71]. Tocotrienols supplementation has also been reported to improve lipid profiles in chronic hemodialysis patients [72].…”