Mice lacking α-tocopherol transfer protein gene have severe α-tocopherol deficiency in multiple regions of the central nervous system

Gohil, Kishorchandra; Oommen, Saji; Quach, Hung T.; Vasu, Vihas T.; Aung, Hnin Hnin; Schock, Bettina; Cross, Carroll E.; Vatassery, Govind T.

doi:10.1016/j.brainres.2008.01.044

Cited by 38 publications

(43 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[39]). It is also interesting to note that significant gender-specific differences in tissue a-tocopherol levels have been reported [52][53][54]. We suggest that potential interaction effects between vitamin E supplementation and other experimental variables require further investigation in light of these reported findings.…”

Section: Impact Of Vitamin E Supplementation On Rodent Lifespanmentioning

confidence: 86%

Vitamin E supplementation and mammalian lifespan

Banks¹,

Speakman²,

Selman³

2010

Molecular Nutrition Food Res

View full text Add to dashboard Cite

Vitamin E refers to a family of several compounds that possess a similar chemical structure comprising a chromanol ring with a 16-carbon side chain. The degree of saturation of the side chain, and positions and nature of methyl groups designate the compounds as tocopherols or tocotrienols. Vitamin E compounds have antioxidant properties due to a hydroxyl group on the chromanol ring. Recently, it has been suggested that vitamin E may also regulate signal transduction and gene expression. We previously reported that lifelong dietary vitamin E (alpha-tocopherol) supplementation significantly increased median lifespan in C57BL/6 mice by 15%. This lifespan extension appeared to be independent of any antioxidant effect. Employing a transcriptional approach, we suggest that this increase in lifespan may reflect an anti-cancer effect via induction of the P21 signalling pathway, since cancer is the major cause of death in small rodents. We suggest that the role of this pathway in life span extension following supplementation of vitamin E now requires further investigation.

show abstract

Section: Impact Of Vitamin E Supplementation On Rodent Lifespanmentioning

confidence: 86%

Vitamin E supplementation and mammalian lifespan

Banks¹,

Speakman²,

Selman³

2010

Molecular Nutrition Food Res

View full text Add to dashboard Cite

show abstract

“…Interestingly, following just one week of development, the adult pattern was already established for ascorbate and α-tocopherol in the P14 brain with few exceptions. Overall, these results can be explained by the developmental stage of a brain region, such as the varying neuronal and glial densities and the stage of myelination at a given postnatal age [15, 16, 19]. However, this is unlikely to be the sole explanation, as discussed below.…”

Section: Discussionmentioning

confidence: 99%

“…The litter size was culled to eight on P3. Only males were studied, in order to avoid the confounding effects of sex on the antioxidants [16, 25]. Animals in Aim 1 were killed after overnight fasting (n=6 at P14 and P60, and n=14 at P7).…”

Section: Methodsmentioning

confidence: 99%

“…The brain was removed and the following nine regions were dissected as previously described [7, 16]: olfactory bulb, cerebral cortex, hippocampus, striatum, hypothalamus (anterior brain regions), cerebellum, pons, medulla oblongata (posterior brain regions) and midbrain. The tissue samples were manually homogenized and extractions for ascorbate and GSH analyses were performed immediately.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Changes in ascorbate, glutathione and α-tocopherol concentrations in the brain regions during normal development and moderate hypoglycemia in rats

Rao

Quach

Smith

et al. 2014

Neuroscience Letters

Self Cite

View full text Add to dashboard Cite

Ascorbate, glutathione and α-tocopherol are the major low molecular weight antioxidants in the brain. The simultaneous changes in these compounds during normal development, and under a pro-oxidant condition are poorly understood. Ascorbate, glutathione and α-tocopherol concentrations in the olfactory bulb, cerebral cortex, hippocampus, striatum, hypothalamus, midbrain, cerebellum, pons and medulla oblongata were determined in postnatal day (P) 7, P14 and P60 male rats. A separate group of P14 and P60 rats were subjected to acute hypoglycemia, a pro-oxidant condition, prior to tissue collection. The concentrations of all three antioxidants were 100-600% higher in the brain regions at P7 and P14, relative to P60. The neuron-rich anterior brain regions (cerebral cortex and hippocampus) had higher concentrations of all three antioxidants than the myelin-rich posterior regions (pons and medulla oblongata) at P14 and P60. Hypoglycemia had a differential effect on the antioxidants. Glutathione was decreased at both P14 and P60. However, the decrease was localized at P14 and global at P60. Hypoglycemia had no effect on ascorbate and α-tocopherol at either age. Higher antioxidant concentrations in the developing brain may reflect the risk of oxidant stress during the early postnatal period and explain the relative resistance to oxidant-mediated injury at this age.

show abstract

“…After atocopherol enters the brain, aTTP may have an important role in supplying a-tocopherol to neurons and glial cells. We and others showed that a-tocopherol in the brain was almost depleted in aTTP -/-mice and was markedly decreased even in aTTP -/-mice fed an a-tocopherol-rich diet resulting in increased serum a-tocopherol (Yokota et al, 2001;Gohil et al, 2008). aTTP is expressed in astrocytes (Hosomi et al, 1998), and cholesterol, as a major lipid, is transferred to neurons and glial cells from astrocytes by HDL-like particles synthesized in astrocytes (Pfrieger, 2003;Vance et al, 2005;Herz and Chen, 2006).…”

Section: Introductionmentioning

confidence: 99%

High-Density Lipoprotein FacilitatesIn VivoDelivery of α-Tocopherol–Conjugated Short-Interfering RNA to the Brain

et al. 2011

View full text Add to dashboard Cite

We originally reported the use of vitamin E (a-tocopherol) as an in vivo vector of short-interfering RNA (siRNA) to the liver. Here, we apply our strategy to the brain. By combining high-density lipoprotein (HDL) as a second carrier with a-tocopherol-conjugated siRNA (Toc-siRNA) in the brain, we achieved dramatic improvement of siRNA delivery to neurons. After direct intracerebroventricular (ICV) infusion of Toc-siRNA/HDL for 7 days, extensive and specific knock-down of a target gene, b-site amyloid precursor protein cleaving enzyme 1 (BACE1), was observed in both mRNA and protein levels, especially in the cerebral cortex and hippocampus. This new delivery method achieved a much more prominent down-regulation effect than conventional silencing methods of the brain gene, i.e., ICV infusion of nonconjugated siRNA or oligonucleotides. With only 3 nmol Toc-siRNA with HDL, BACE1 mRNA in the parietal cortex could be reduced by *70%. We suppose that this dramatic improvement of siRNA delivery to the brain is due to the use of lipoprotein receptor-mediated endocytosis because the silencing efficiency was significantly increased by binding of Toc-siRNA to the lipoprotein, and in contrast, was clearly decreased in lipoprotein-receptor knockout mice. These results suggest exogenous siRNA could be used clinically for otherwise incurable neurological diseases.

show abstract

Mice lacking α-tocopherol transfer protein gene have severe α-tocopherol deficiency in multiple regions of the central nervous system

Cited by 38 publications

References 61 publications

Vitamin E supplementation and mammalian lifespan

Vitamin E supplementation and mammalian lifespan

Changes in ascorbate, glutathione and α-tocopherol concentrations in the brain regions during normal development and moderate hypoglycemia in rats

High-Density Lipoprotein FacilitatesIn VivoDelivery of α-Tocopherol–Conjugated Short-Interfering RNA to the Brain

Contact Info

Product

Resources

About