Vitamin transporters in mice brain with aging

J Anat. 2018 Apr;232(4):699-715. doi: 10.1111/joa.12769. Epub 2018 Jan 8.

Abstract

Its high metabolic rate and high polyunsaturated fatty acid content make the brain very sensitive to oxidative damage. In the brain, neuronal metabolism occurs at a very high rate and generates considerable amounts of reactive oxygen species and free radicals, which accumulate inside neurons, leading to altered cellular homeostasis and integrity and eventually irreversible damage and cell death. A misbalance in redox metabolism and the subsequent neurodegeneration increase throughout the course of normal aging, leading to several age-related changes in learning and memory as well as motor functions. The neuroprotective function of antioxidants is crucial to maintain good brain homeostasis and adequate neuronal functions. Vitamins E and C are two important antioxidants that are taken up by brain cells via the specific carriers αTTP and SVCT2, respectively. The aim of this study was to use immunohistochemistry to determine the distribution pattern of these vitamin transporters in the brain in a mouse model that shows fewer signs of brain aging and a higher resistance to oxidative damage. Both carriers were distributed widely throughout the entire brain in a pattern that remained similar in 4-, 12-, 18- and 24-month-old mice. In general, αTTP and SVCT2 were located in the same regions, but they seemed to have complementary distribution patterns. Double-labeled cell bodies were detected only in the inferior colliculus, entorhinal cortex, dorsal subiculum, and several cortical areas. In addition, the presence of αTTP and SVCT2 in neurons was analyzed using double immunohistochemistry for NeuN and the results showed that αTTP but not SVCT2 was present in Bergmann's glia. The presence of these transporters in brain regions implicated in learning, memory and motor control provides an anatomical basis that may explain the higher resistance of this animal model to brain oxidative stress, which is associated with better motor performance and learning abilities in old age.

Keywords: aging; antioxidants; oxidative damage; transporters; vitamin C; vitamin E.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Antigens, Nuclear / metabolism
  • Antioxidants / metabolism
  • Ascorbic Acid / metabolism
  • Biomarkers / metabolism
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Carrier Proteins / metabolism*
  • Glial Fibrillary Acidic Protein / metabolism
  • Immunohistochemistry / methods
  • Learning
  • Male
  • Memory
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins / metabolism
  • Neuroglia / metabolism
  • Neuroglia / ultrastructure
  • Neurons / metabolism
  • Neurons / ultrastructure
  • Oxidative Stress*
  • Sodium-Coupled Vitamin C Transporters / metabolism*
  • Vitamin E / metabolism

Substances

  • Antigens, Nuclear
  • Antioxidants
  • Biomarkers
  • Carrier Proteins
  • GFAP protein, human
  • Glial Fibrillary Acidic Protein
  • Nerve Tissue Proteins
  • Slc23a2 protein, mouse
  • Sodium-Coupled Vitamin C Transporters
  • alpha-tocopherol transfer protein
  • neuronal nuclear antigen NeuN, human
  • Vitamin E
  • Ascorbic Acid